Incidence and clinical parameters associated with eribulin mesylate-induced peripheral neuropathy

Publication date: Available online 12 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Bin Zhao, Hong Zhao, Jiaxin Zhao
Eribulin mesylate is a microtubule-targeting agent that has been approved for the treatment of breast cancer and liposarcoma. Due to its novel mechanism of action, eribulin therapy induces a distinct profile of adverse events, including peripheral neuropathy. However, the incidence and risk of eribulin-related neurotoxicities are unclear. Here, we conducted a systematic search of PubMed and Embase from their inception to October 2017. Eligible studies included trials in which eribulin was intravenously administered at a standard dose of 1.4 mg/m² over 2-5 minutes on days 1 and 8 on a 21-day cycle. The events of all-grade and high-grade peripheral neuropathy were collected to calculate the overall incidence and relative risk (RR). A total of thirty-two studies containing 6,129 subjects were included in this analysis. The incidences of all-grade and high-grade eribulin monotherapy-related peripheral neuropathy were 28% (95% confidence interval [CI], 24%-32%) and 4% (95% CI, 3%-5%), respectively. Subgroup analysis further revealed that a higher incidence of neurotoxicities was observed in patients with breast cancer and those with longer treatment duration. Moreover, eribulin-treated subjects had a significantly increased risk of all-grade (RR, 2.00; 95% CI, 1.70-2.35; p = 0.008) and high-grade (RR, 3.68; 95% CI, 2.30-5.89; p<0.001) neurotoxicities. Our results suggested that patients treated with eribulin had an increased risk of developing peripheral neuropathy.

Graphical abstract

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Radiation therapy in renal cell carcinoma

Publication date: Available online 12 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Francesca De Felice, Vincenzo Tombolini




https://ift.tt/2JFAOKM

Endonuclease-independent DNA Mismatch Repair Processes on the Lagging Strand

Publication date: Available online 12 June 2018
Source:DNA Repair
Author(s): Eric A. Josephs, Piotr E. Marszalek
DNA mismatch repair (MMR) pathways coordinate the excision and re-synthesis of newly-replicated DNA if a mismatched base-pair has been identified by protein MutS or MutS homologues (MSHs) after replication. DNA excision during MMR is initiated at single-strand breaks (SSBs) in vitro, and several redundant processes have been observed in reconstituted systems which either require a pre-formed SSB in the DNA and/or require a mismatch-activated nicking endonuclease to introduce a new SSB in order to initiate MMR. However, the conditions under which each of these processes may actually occur in living cells have remained obscured by the limitations of current MMR assays. Here we use a novel assay involving chemically-modified oligonucleotide probes to insert targeted DNA 'mismatches' directly into the genome of living bacteria to interrogate their replication-coupled repair processes quantitatively in a strand-, orientation-, and mismatched nucleotide-specific manner. This 'semi-protected oligonucleotide recombination' (SPORE) assay reveals direct evidence in Escherichia coli of an efficient endonuclease-independent MMR process on the lagging strand—a mechanism that has long-since been considered for lagging-strand repair but never directly shown until now. We find endonuclease-independent MMR is coordinated asymmetrically with respect to the replicating DNA—directed primarily from 3′- of the mismatch—and that repair coordinated from 3′- of the mismatch is in fact the primary mechanism of lagging-strand MMR. While further work is required to explore and identify the molecular requirements for this alternative endonuclease-independent MMR pathway, these findings made possible using the SPORE assay are the first direct report of this long-suspected mechanism in vivo.



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Regulation of DNA repair in the absence of classical non-homologous end joining

Publication date: Available online 12 June 2018
Source:DNA Repair
Author(s): Youn-Jung Kang, Catherine T. Yan
Classical non-homologous end-joining (cNHEJ) is the main pathway for the repair of DNA double strand breaks (DSBs) in mammalian cells. In the absence of c-NHEJ, an alternative end-joining (A-EJ) mechanism resolves DSBs. To date, no A-EJ specific factor has been identified. Instead, this mechanism appears to co-opt proteins involved in more than one DNA repair pathway. These include components of base-excision repair (PARP1/XRCC1/LIG3), interstrand cross-link repair (BRCA1/FANCD2), and DSB response/DNA end-resection (MRE11A/RAD50/RBBP8). To clarify the contribution of these factors to A-EJ, here we examined their expression and recruitment to DSBs in correlation with surrogates of cNHEJ (53BP1) and homologous recombination (RAD51) in cells deficient for the cNHEJ end-ligation component XRCC4. This revealed XRCC4-deficient cells exhibited marked increases in the stability of A-EJ transcripts that result in correspondingly elevated levels of associated proteins, in comparison to WT cells. RAD51 was also increased while 53BP1 was unaffected. Treatment with radiomimetic DSB-inducing drug doxorubicin did not influence these activities. However, FANCD2, BRCA1 and XRCC1 foci, prominently associated with 53BP1 foci and hence DSBs resolved by cNHEJ, were only detected in doxorubicin-treated XRCC4-deficient cells. Strikingly, treatment of XRCC4-deficient cells with the PARP-specific inhibitor Niraparib enhanced A-EJ, and substantially induced 53BP1 transcripts and the numbers of A-EJ-associated 53BP1 DNA damage foci. RAD51 was severely inhibited, and upstream cNHEJ (KU70/KU80/DNA-PKCs/ARTEMIS) transcripts were substantially induced. These latter results were recapitulated in BRCA1-deficient cells, which contrastingly did not affect 53BP1 or PARP1 status irrespective of doxorubicin or Niraparib treatment. Hence A-EJ is regulated transcriptionally, reduced by a higher turnover rate in cNHEJ-proficient cells and sustained but fine-tuned by PARP1 in XRCC4-deficient cells to promote DNA repair and survival. Upstream cNHEJ components are similarly transcriptionally down-modulated by PARP1 and BRCA1 in a manner inversely correlated with HR and mechanistically distinct from A-EJ respectively in cNHEJ-deficient and cNHEJ-proficient settings.



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Patterns of disease control and survival in patients with melanoma brain metastases undergoing immune-checkpoint blockade

Publication date: August 2018
Source:European Journal of Cancer, Volume 99
Author(s): Laura Milsch, Anja Gesierich, Sophia Kreft, Elisabeth Livingstone, Lisa Zimmer, Matthias Goebeler, Dirk Schadendorf, Bastian Schilling
ObjectivesImmune-checkpoint blockers (ICBs) significantly prolong overall survival (OS) in patients with advanced melanoma. Limited data are available on the efficacy and clinical benefit in patients with melanoma brain metastases (MBMs). The aim of this study was to determine whether ICB is active in an unselected cohort treated of patients with known brain metastases and if disease control correlates with the survival.MethodsA total of 385 patients with metastatic malignant melanoma treated with ICB as monotherapy between 2005 and 2017 in two tertiary referral centres were included. Patient records were searched for the development of brain metastases. Demographic and clinical data of all patients were collected retrospectively.ResultsWe identified 177 patients with MBM who received ICBs (ipilimumab, nivolumab, pembrolizumab). Patients with and without brain metastases received similar ICB regimens. Prognosis was inferior in patients with brain metastases; patients with >1 brain metastasis showed even poorer survival. For extracranial (ec) metastases, disease control was associated with improved survival. However, when comparing patients with intracranial (ic) disease control during immunotherapy to patients with ic disease progression, no difference in OS could be observed.ConclusionsIn our study, ec disease control was the dominant predictive factor for OS in both patients with or without melanoma brain metastases. These data indicate that clinical trials in melanoma patients with brain metastases should address end-points such as symptom control, quality of life or OS in addition to ic response rates.



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Scholar : These new articles for Critique: Studies in Contemporary Fiction are available online

The online platform for Taylor & Francis Online content New for Critique: Studies in Contemporary Fiction and online now on Taylor & Francis Online: Original Articles "Evidence": Garth Risk Hallberg's City on Fire, the Gutenberg Parenthesis, and Generation X at Midlife Brian Glover Pages: 1-17 | DOI: 10.1080/00111619.2018.1432559 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Data on the evaluation of structural index from aeromagnetic enhanced datasets with the application of Euldph-λ semi-automatic algorithm

Publication date: August 2018
Source:Data in Brief, Volume 19
Author(s): John Stephen Kayode, Yusri Yusup
A secondary dataset was generated from the Euldph-λ semi-automatic Algorithm, (ESA) developed to automatically computes various depths to the magnetic anomalies using a primary data set from gridded aeromagnetic data obtained in the study area. Euler Deconvolution techniques, (EDT), was adopted in the identification and definition of the magnetic anomaly source rocks in the study area. The aim is to use the straightforward technique to pinpoint magnetic anomalies at a depth which substantiate mineralization potential of the area. The ESA was integrated with the imaging function of Oasis Montaj 2014 source parameter from Geosoft® Inc. From the data, it could be summarized that similar tectonic processes during the deformation and metamorphic activities, the subsurface structures of the study area produce corresponding trending form.



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Fusarium graminearum 1H NMR metabolomics

Publication date: August 2018
Source:Data in Brief, Volume 19
Author(s): A. Sevastos, I.F. Kalampokis, A. Panagiotopoulou, M. Pelecanou, K.A. Aliferis
Raw ¹H NMR spectra of Fusarium graminearum hyphae can be found at the website of the pesticide metabolomics group (PMG) of the Agricultural University of Athens at the address: https://ift.tt/2l6wNVf, accession number PMG-01–17. The data set support the research article "Implication of Fusarium graminearum Primary Metabolism in its Resistance to Benzimidazole Fungicides as revealed by ¹H NMR Metabolomics" [1].



https://ift.tt/2t3zUAV

Data on lithofacies, sedimentology and palaeontology of South Rifian Corridor sections (Morocco)

Publication date: August 2018
Source:Data in Brief, Volume 19
Author(s): W. Capella, N. Barhoun, R. Flecker, F.J. Hilgen, T. Kouwenhoven, L.C. Matenco, F.J. Sierro, M.A. Tulbure, M.Z. Yousfi, W. Krijgsman
We provide lithological, sedimentological and micropalaeontological descriptions of 39 sections and boreholes crossing the upper Miocene deposits of the Rifian Corridor. These deposits represent the sedimentary remnants of the marine gateway that connected the Atlantic to the Mediterranean in the late Miocene. Results from these 39 sites were adopted to reconstruct the palaeogeographic evolution of the gateway presented in the associated research article (Capella et al., 2018) [1]. For each outcrop we present a synthesis of field observations, lithofacies, key sedimentological features, planktic and benthic assemblages.



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Lithostratigraphic and magnetostratigraphic data from late Cenozoic glacial and proglacial sequences underlying the Altiplano at La Paz, Bolivia

Publication date: August 2018
Source:Data in Brief, Volume 19
Author(s): Nicholas J. Roberts, René W. Barendregt, John J. Clague
We provide lithostratigraphic and magnetostratigraphic data derived from a Plio-Pleistocene continental sediment sequence underlying the Altiplano plateau at La Paz, Bolivia. The record comprises six sections along the upper Río La Paz valley, totaling over one kilometre of exposure and forming a ~20-km transect oblique to the adjacent Cordillera Real. Lithostratigraphic characterization includes lithologic and stratigraphic descriptions of units and their contacts. We targeted gravel and diamicton units for paleomagnetic sampling to address gaps in the only previous magnetostratigraphic study from this area. Paleomagnetic data – magnetic susceptibility and primary remanent magnetization revealed by progressive alternating field demagnetization – are derived from 808 individually oriented samples of flat-lying, fine-grained sediments. The datasets enable characterization of paleo-surfaces within the sequence, correlation between stratigraphic sections, and differentiation of asynchronous, but lithologically similar units. Correlation of the composite polarity sequence to the geomagnetic polarity time scale supports a range of late Cenozoic paleoenvironmental topics of regional to global importance: the number and ages of early glaciations in the tropical Andes; interhemispheric comparison of paleoclimate during the Plio-Pleistocene climatic transition; timing of and controls on inter-American faunal exchange; and the variability of Earth's paleomagnetic field.



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Students’ participation in Hult Prize and their decision for entrepreneurship: Data gathered from Hult Prize 2018 regional finals in Nigeria

Publication date: August 2018
Source:Data in Brief, Volume 19
Author(s): Stephen Oluwatobi, Damilare Oshokoya, Aderemi Atayero, Olumuyiwa Oludayo, Colette Nsofor, Adeola Oyebode
This data article is an expression of data that reflects how students' participation in the Hult Prize 2018 regional finals affects their decision to become entrepreneurs. The primary data was sourced using a questionnaire developed with Google doc form. Out of 120 students that participated in the Hult Prize 2018 regional finals in Nigeria, 103 of them responded. Their responses are as presented in this article. Such will be relevant to researchers who want to find out why students desire to become entrepreneurs and the best approach and timing to enable them.



https://ift.tt/2t26EKM

Paleotemperature, geochemical and grain size data in Quaternary sediments from the Gloria Drift (Northwest Atlantic)

Publication date: August 2018
Source:Data in Brief, Volume 19
Author(s): Leyla Bashirova, Evgenia Dorokhova, Vadim Sivkov, Ekaterina Novichkova
Data file presents information on the variation in sea surface temperatures (SST), as well as geochemical (e.g. stable isotope, calcium carbonate), micropaleontological and grain size data from the Gloria Drift (Northwest Atlantic). The data are obtained from the three marine sediment gravity core sections (AMK-4493, AI-3646 and AI-3415) which were formed during Quaternary period. Dataset contains SST values (winter and summer: 0–50 water layer) and ice-rafted debris (IRD) counts, each in 308 samples; stable isotope data (δ¹⁸O and δ¹³C) from 235 samples; calcium carbonate content from 351 samples; relative abundance of polar species of planktonic foraminifera Neogloboquadrina pachyderma (sinistral) (Ehrenberg) in 51 samples, data of grain size analysis in bulk sediments (123 samples) and carbonate-free sediments (664). These data provide information about conditions of sedimentation at the Gloria Drift area.



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Geoelectrical resistivity data set for characterising crystalline basement aquifers in Basiri, Ado-Ekiti, southwestern Nigeria

Publication date: August 2018
Source:Data in Brief, Volume 19
Author(s): Ahzegbobor P. Aizebeokhai, Olubukola Ogungbade, Kehinde D. Oyeyemi
This article consists of data sets for thirty (30) vertical electrical sounding (VES) and four (4) traverses of 2D electrical resistivity imaging (ERI) collected within, Ado-Ekiti, southwestern Nigeria using an ABEM Terrameter (SAS 1000/4000) system. Win-Resist computer program was used to process the apparent resistivity data sets for the VES to determine the geoelectric layers and their respective parameters (resistivity and thickness). The observed data sets for the 2D ERI were processed using RES2DINV software to obtain 2D inverse model resistivity distribution of the subsurface. The resistivity soundings and the 2D ERI were combined to delineate and characterise the crystalline basement features associated with basement aquifers.



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Survey dataset on analysis of queues in some selected banks in Ogun State, Nigeria

Publication date: August 2018
Source:Data in Brief, Volume 19
Author(s): Sheila A. Bishop, Hilary I. Okagbue, Pelumi E. Oguntunde, Abiodun A. Opanuga, Oluwole A. Odetunmibi
Queuing theory is the mathematical study of waiting queues (or lines). The theory enables the mathematical analysis of several related processes such as arriving at the queue, waiting in line and being served by a server. This data article contains the analysis of queuing systems obtained from queues from the observed data of some selected banks in Ogun State. One of the gains expected from this survey, is to help review the efficiency of the models used by banks in such geographical locations in sub-Saharan countries. The Survey attempts to estimate the average waiting time and length of queue(s).



https://ift.tt/2l6wMRb

Loss of Trem2 in microglia leads to widespread disruption of cell coexpression networks in mouse brain

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Guillermo Carbajosa, Karim Malki, Nathan Lawless, Hong Wang, John W. Ryder, Eva Wozniak, Kristie Wood, Charles A. Mein, Richard J.B. Dobson, David A. Collier, Michael J. O'Neill, Angela K. Hodges, Stephen J. Newhouse
Rare heterozygous coding variants in the triggering receptor expressed in myeloid cells 2 (TREM2) gene, conferring increased risk of developing late-onset Alzheimer's disease, have been identified. We examined the transcriptional consequences of the loss of Trem2 in mouse brain to better understand its role in disease using differential expression and coexpression network analysis of Trem2 knockout and wild-type mice. We generated RNA-Seq data from cortex and hippocampus sampled at 4 and 8 months. Using brain cell-type markers and ontology enrichment, we found subnetworks with cell type and/or functional identity. We primarily discovered changes in an endothelial gene-enriched subnetwork at 4 months, including a shift toward a more central role for the amyloid precursor protein gene, coupled with widespread disruption of other cell-type subnetworks, including a subnetwork with neuronal identity. We reveal an unexpected potential role of Trem2 in the homeostasis of endothelial cells that goes beyond its known functions as a microglial receptor and signaling hub, suggesting an underlying link between immune response and vascular disease in dementia.



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Reflections on the Boston Marathon from a Breast Cancer Oncologist (or, Why I Just Don't Quit)

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Frontline Treatment for Older Patients with Mantle Cell Lymphoma

AbstractThe natural history of mantle cell lymphoma (MCL) undergoing chemotherapy is a cyclical pattern of remission followed by recurrence of disease due to acquired chemotherapy resistance. The median age of the occurrence of MCL is 65 years, so half of the newly diagnosed MCL patients are considered "elderly." The tolerance to long‐term chemotherapy in elderly patients is decreased; hence, the response to frontline therapy used is of paramount importance. We hope that our review may guide clinicians in treating such populations in a more personalized and evidence‐based manner.In the older patients with risk variables, frontline treatment is determined according to different body status of fit, unfit or compromised, and frail. In the fit patients, the pursuit of remission and prolongation of survival might currently justify the use of more intense and toxic therapies. For unfit or compromised older patients, disease control needs to be prioritized, maintaining a balance between the benefits and toxicities of the treatment. For frail patients, tolerance of treatment and minimizing myelotoxicity should be the primary focus. "Chemotherapy‐free" regimens are likely to be considered as the first‐line strategy for this population. On the other hand, in the older MCL population without risk variables, observation or "watch and wait" can prevent overtreatment. Furthermore, more clinical trials and research studies on novel agents and targeted therapies need to be translated into the general population to provide optimal treatment and to guide personalized treatment.Implications for Practice.This review emphasizes the importance of frontline therapies for older MCL patients. MCL patients commonly experience a cyclical pattern of remission followed by recurrence of disease due to acquired chemotherapy resistance. As a special population, elderly patients have various comorbidities and decreased organ function, which may reduce the chances of undergoing treatment for recurrent disease. Thus, this older population of patients with MCL should be treated separately and exceptionally. So far, systematic reviews with regard to frontline treatment for older patients with MCL have not been encountered, but the hope is that this review may guide clinicians in treating such populations in a more personalized and evidence‐based manner.

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Tumor Lysis Syndrome in the 21st Century: To Recreate Risk Factors and Prognosis?

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Pertuzumab: Getting the Balance Right

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Pattern and Predictors of Outpatient Palliative Care Referral Among Thoracic Medical Oncologists

AbstractBackground.There is significant variation in access to palliative care. We examined the pattern of outpatient palliative care referral among thoracic medical oncologists and identified oncologist characteristics associated with greater referral.Materials and Methods.We retrieved data on all patients who died of advanced thoracic malignancies at our institution between January 1, 2007, and December 31, 2012. Using median as a cutoff, we defined two groups (high‐referring and low‐referring oncologists) based on their frequency of referral. We examined various oncologist‐ and patient‐related characteristics associated with outpatient referral.Results.Of 1,642 decedents, 444 (27%) had an outpatient palliative care referral. The median proportion of referral among 26 thoracic oncologists was 30% (range 9%–45%; median proportion of high‐referring 37% vs. low‐referring 24% when divided into two groups at median). High‐referring oncologists were significantly younger (age 45 vs. 56) than low‐referring oncologists; they were also significantly more likely to refer patients earlier (median interval between oncology consultation and palliative care consultation 90 days vs. 170 days) and to refer those without metastatic disease (7% vs. 2%). In multivariable mixed‐effect logistic regression, younger oncologists (odds ratio [OR] = 0.97 per year increase, 95% confidence interval [CI] 0.95–0.995), younger patients (OR = 0.98 per year increase, 95% CI 0.97–0.99), and nonmetastatic disease status (OR = 0.48, 95% CI 0.29–0.78) were significantly associated with outpatient palliative care referral.Conclusion.The pattern of referral to outpatient palliative care varied widely among thoracic oncologists. Younger oncologists were not only referring a higher proportion of patients, but also referring patients earlier in the disease trajectory.Implications for Practice.This retrospective cohort study found that younger thoracic medical oncologists were significantly more likely to refer patients to outpatient palliative care and to do so earlier in the disease trajectory compared with older oncologists, even after adjusting for other known predictors such as patient demographics. The findings highlight the role of education to standardize palliative care access and imply that outpatient palliative care referral is likely to continue to increase with a shifting oncology workforce.

https://ift.tt/2t2RLYx