To what extent is alcohol consumption associated with breast cancer recurrence and second primary breast cancer?: A systematic review

Publication date: Available online 20 September 2016
Source:Cancer Treatment Reviews
Author(s): Phanthira Simapivapan, Anna Boltong, Allison Hodge
BackgroundThe association between alcohol intake and breast cancer recurrence or development of second primary breast cancer in the survivor population is unclear. The aim of this systematic review was to evaluate the existing evidence to assess the extent to which alcohol consumption is associated with breast cancer recurrence and second primary breast cancer.MethodsSix databases (Cochrane Library, EMBASE, MEDLINE, PubMed, Scopus and Web of Science) were searched using the following search phrase: (breast cancer OR breast adenocarcinoma OR breast neoplasm OR breast tumor) AND (alcohol^∗ OR alcohol intake OR alcohol consumption OR ethanol) AND (recurrence OR second primary). A narrative synthesis was conducted on studies meeting the inclusion criteria.ResultsAfter screening, 16 studies met the inclusion criteria, of which 11 assessed breast cancer recurrence and 5 assessed second primary breast cancer. Considerable clinical and methodological heterogeneity was observed between studies. Approximately half of the included studies observed a modest, but significant, association between alcohol consumption and increased risk of breast cancer recurrence or development of a second primary breast cancer, with some studies observing associations from as little as six grams of alcohol intake per day. Two studies suggest this association was stronger in postmenopausal women.ConclusionThere is some evidence that alcohol consumption increases the risk of breast cancer recurrence, particularly in postmenopausal women. The association between alcohol and development of a second primary breast cancer is less clear. Inconsistencies in methodology and results across studies complicate attempts to develop a cohesive interpretation of findings.



http://ift.tt/2d8qkbk

Mechanism of drug resistance in relation to site of metastasis: Meta-analyses of randomized controlled trials in advanced breast cancer according to anticancer strategy

Publication date: Available online 20 September 2016
Source:Cancer Treatment Reviews
Author(s): Saroj Niraula, Alberto Ocana
BackgroundBreast cancer is heterogeneous at different levels: biologic subtypes, intratumoral areas, and sites of metastases. Randomized controlled trials (RCTs) classify metastatic sites as visceral or non-visceral, but this has little influence in treatment decisions, particularly in the absence of clinical urgency. Indeed, it is unclear if response to treatments differs among sites of metastases.Patients and MethodsRCTs investigating 3 different anticancer strategies in metastatic breast cancer were identified: (1) new hormonal therapy, (2) new targeted therapies in hormone receptor positive tumours (everolimus or palbociclib), and (3) new anti-HER2 therapies. RCTs reporting hazard ratios (HR) for Progression Free Survival (PFS) and Overall Survival (OS) for sub-groups based on sites of metastases were weighted using generic inverse variance approach, and pooled in meta-analyses using Revman 5.3. Subgroup difference was tested with Chi² statistics.ResultsEleven RCTs (6,701 pts.) qualified. There was a significant difference in PFS between women with visceral versus non-visceral metastases when two endocrine strategies were compared, with benefits limited to women with visceral metastases [Pooled HR 0.85; 95% CI, 0.77-0.95 versus 1.02(0.88-1.18) for non-visceral; p(difference)=0.05]. However, combination of an endocrine therapy and a targeted therapy was associated with better PFS compared to endocrine therapy alone for both groups [HR 0.51(0.43-0.60) versus 0.45(0.36-0.56) for non-visceral; p(difference)=0. 36]. Novel HER-2 targeted therapies were associated with significantly better PFS and OS only in visceral metastases [HR 0.59 (0.52-0.66) versus 0.71(0.44-1.13) for non-visceral, p(difference)=0.45, for PFS; and 0.64 (0.56-0.73) versus 0.82 (0.57=1.19) for non-visceral, p(difference)=0.20, for OS].ConclusionCombination of targeted agents and endocrine therapy results in concordant, superior PFS suggesting targetable endocrine resistance across metastatic sites. Discordant responses with endocrine strategy alone support use of targeted therapy, rather than change in endocrine agent at disease progression. HER2 targeted therapies may be less effective in areas of poor vascularization.



http://ift.tt/2cAyK6r

The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Publication date: December 2016
Source:Neurobiology of Aging, Volume 48
Author(s): Claire Lancaster, Naji Tabet, Jennifer Rusted
Possession of an Apolipoprotein E (APOE) e4 allele is an established risk factor for Alzheimer's disease, whereas the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. Sixty-six volunteers, aged 45–55 years, completed 3 tasks that provided complementary measures of attentional control: prospective memory, sustained attention, and inhibition. Performance was compared between e2 carriers, e4 carriers, and e3 homozygotes (the population norm). Carriers of the e4 allele showed subtle disadvantages, compared with the e3 group, in accuracy of Stroop task and prospective memory performance. Contrary to expectations, e2 carriers showed performance disadvantages in sustained attention. The finding of detrimental effects in attentional control for both e4 and e2 complicates the current model that proposes opposing effects of these variants on later-life cognition. Future research is needed to understand how cognitive differences develop with increasing age, and the physiological mechanisms that underpin these changes.



http://ift.tt/2cQXgjv

In silico, in vitro and case-control analyses as an effective combination for analyzing BRCA1 and BRCA2 unclassified variants in a population-based sample

Publication date: Available online 20 September 2016
Source:Cancer Genetics
Author(s): Marta Rodríguez-Balada, Bàrbara Roig, Lourdes Martorell, Mireia Melé, Mònica Salvat, Elisabet Vilella, Joan Borràs, Josep Gumà
Ascertaining the clinical consequences of BRCA1 and BRCA2 variants of uncertain significance (VUS) is currently indispensable for providing effective genetic counseling and preventive actions for families with hereditary breast and ovarian cancer (HBOC). To this end, we conducted a combination of in silico prediction and cDNA splicing analyses of 13 BRCA1 and 10 BRCA2 VUS identified in our cohort as well as a case-control analysis in a population-based sample of 10 recurrent VUS. We observed consistent results between the in silico predictions and sequencing analyses for all analyzed VUS. An abnormal cDNA pattern was observed for variants c.212+1G>A and c.5278-1G>A in BRCA1 and c.516+2T>A and c.8168A>G in BRCA2 according to in silico splicing prediction.. A case-control study of VUS confirmed the polymorphisms of the c.67+62A>G, c.7008-62A>G and c.8851G>A BRCA2 variants previously published. c.4068G>A in the BRCA2 gene can also be considered a polymorphism due to its occurrence at a frequency greater than 1% in our population.Our study shows that employing population-based analysis and a combination of several in silico methods yields highly accurate information, resulting in a reliable tool for selecting variants for cDNA sequencing analysis in routine cancer genetic counseling units.



http://ift.tt/2d1YZHr

Scholar : These new articles for The American Journal of Family Therapy are available online

The online platform for Taylor & Francis Online content New for The American Journal of Family Therapy and online now on Taylor & Francis Online: Original Articles Emotionally Focused Couple Therapy With Neurodegenerative Diseases: A Pilot Study Simona Ghedin, Alberto Semi, Floriana Caccamo, Luca Caldironi, Cristina Marogna, Francesco Piccione, Rosaria Stabile, Rita Lorio & Giulio Vidotto Pages: 1-12 | DOI: 10.1080/01926187.2016.1223562 Read our collection of free articles created as a companion to the BPS PsychCrunch podcast. This message is personalised to your status as a society member. Please do not forward this email. To recommend content, please use the social sharing tools on the website. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert 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.

Novel Insights into PML-Dependent Oncosuppression

Publication date: Available online 20 September 2016
Source:Trends in Cell Biology
Author(s): Lorenzo Galluzzi
At odds with its nuclear counterpart, extranuclear promyelocytic leukemia constitutively inhibits autophagy, hence limiting cancer progression. These data raise the interesting possibility that some tumor suppressors have become specialized to operate at multiple subcellular compartments for counteracting different aspects of the oncogenic process.



http://ift.tt/2d5qoo3

N-cadherin regulates beta-catenin signal and its misexpression perturbs commissural axon projection in the developing chicken spinal cord

Abstract

N-cadherin is a calcium-sensitive cell adhesion molecule that plays an important role in the formation of the neural circuit and the development of the nervous system. In the present study, we investigated the function of N-cadherin in cell–cell connection in vitro with HEK293T cells, and in commissural axon projections in the developing chicken spinal cord using in ovo electroporation. Cell–cell connections increased with N-cadherin overexpression in HEK293T cells, while cell contacts disappeared after co-transfection with an N-cadherin-shRNA plasmid. The knockdown of N-cadherin caused the accumulation of β-catenin in the nucleus, supporting the notion that N-cadherin regulates β-catenin signaling in vitro. Furthermore, N-cadherin misexpression perturbed commissural axon projections in the spinal cord. The overexpression of N-cadherin reduced the number of axons that projected alongside the contralateral margin of the floor plate, and formed intermediate longitudinal commissural axons. In contrast, the knockdown of N-cadherin perturbed commissural axon projections significantly, affecting the projections alongside the contralateral margin of the floor plate, but did not affect intermediate longitudinal commissural axons. Taken together, these findings suggest that N-cadherin regulates commissural axon projections in the developing chicken spinal cord.

http://ift.tt/2d5o14q

Receding Gums: Treatment Options and Causes

Gingival recession is when the gum tissue covering the root of the tooth is pushed back. Learn about its causes and forms of treatment with this article.

http://ift.tt/2crs9NP

Human tolerogenic dendritic cells generated with protein kinase C inhibitor are optimal for functional regulatory T cell induction – A comparative study

Publication date: Available online 19 September 2016
Source:Clinical Immunology
Author(s): Endy Adnan, Takuya Matsumoto, Jun Ishizaki, Sachiko Onishi, Koichiro Suemori, Masaki Yasukawa, Hitoshi Hasegawa
Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. We compared the tolerogenic properties of tDCs treated with protein kinase C inhibitor (PKCI), dexamethasone, vitamin D3 (Vit D3), rapamycin (Rapa), interleukin (IL)-10, transforming growth factor (TGF)-β, and a combination of peroxisome proliferator-activated receptor γ agonist and retinoic acid. All tDCs had a semi-mature DC phenotype. PKCI-, TGF-β-, and Rapa-tDCs showed CCR7 expression and migration to CCL19, but other tDCs showed little or none. PKCI- and IL-10-tDCs induced functional regulatory T cells more strongly than other tDCs. The tolerogenic properties of all tDCs were stable against proinflammatory stimuli. Furthermore, PKCI-tDCs were generated from patients with rheumatoid arthritis and primary Sjögren's syndrome. Therefore, PKCI-tDCs showed the characteristics best suited for tolerance-inducing therapy.



http://ift.tt/2cQN9uY

Long-term Outcomes of Superficial Esophageal Squamous Cell Carcinoma

Condition:   Esophageal Neoplasms
Intervention:  
Sponsors:   Shanghai Zhongshan Hospital;   The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School;   Tongji Hospital;   The affiliated Hospital of Shihezi University
Not yet recruiting - verified September 2016

http://ift.tt/2cOAeve

Endostar Combined With Concurrent Chemoradiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma

Condition:   Nasopharyngeal Carcinoma
Interventions:   Drug: Endostar;   Drug: DDP
Sponsor:   First Affiliated Hospital of Guangxi Medical University
Not yet recruiting - verified September 2016

http://ift.tt/2d1RKiR

Ontario-wide Cancer TArgeted Nucleic Acid Evaluation

Conditions:   Breast Cancer;   Lung Cancer;   Colorectal Cancer;   Melanoma;   Gynecological Cancer;   Genitourinary Cancer;   Pancreatobiliary Cancer;   Gastrointestinal Cancer;   Head and Neck Cancer;   Rare Cancer;   Unknown Primary Cancer
Intervention:  
Sponsors:   University Health Network, Toronto;   Princess Margaret Hospital, Canada
Recruiting - verified September 2016

http://ift.tt/2cOAmuE

Potentiation of Cisplatin-based Chemotherapy by Digoxin in Advanced Unresectable Head and Neck Cancer Patients

Condition:   Head and Neck Cancer
Intervention:   Drug: Digoxin
Sponsors:   Assistance Publique - Hôpitaux de Paris;   Cancer Research and Personalized Medicine (Carpem);   Laboratoire d'excellence en immuno-oncologie (Labex)
Not yet recruiting - verified June 2016

http://ift.tt/2d1RoZD

Synthesis and Structure–Activity Relationships of 1-Benzylindane Derivatives as Selective Agonists for Estrogen Receptor Beta

Publication date: Available online 20 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Shigeru Yonekubo, Nobuhiko Fushimi, Takashi Miyagi, Osamu Nakanishi, Kenji Katsuno, Motoyasu Ozawa, Chiaki Handa, Noritaka Furuya, Hideyuki Muranaka
The estrogen receptor beta (ERβ) selective agonist is considered a promising candidate for the treatment of estrogen deficiency symptoms in ERβ-expressing tissues, without the risk of breast cancer, and multiple classes of compounds have been reported as ERβ selective agonists. Among them, 6-6 bicyclic ring-containing structures (e.g., isoflavone phytoestrogens) are regarded as one of the cyclized analogues of isobutestrol 5b, and suggest that other cyclized scaffolds comprising 5-6 bicyclic rings could also act as selective ERβ ligands.In this study, we evaluated the selective ERβ agonistic activity of 1-(4-hydroxybenzyl)indan-5-ol 7a and studied structure–activity relationship (SAR) of its derivatives. Some functional groups improved the properties of 7a; introduction of a nitrile group on the indane-1-position resulted in higher selectivity for ERβ (12a), and further substitution with a fluoro or a methyl group to the pendant phenyl ring was also preferable (12b, d, and e). Subsequent chiral resolution of 12a identified that R-12a has a superior profile over S-12a. This is comparable to diarylpropionitrile (DPN) 5c, one of the promising selective ERβ agonists and indicates that this indane-based scaffold has the potential to provide better ERβ agonistic probes.

Graphical abstract

http://ift.tt/2d5j6AJ

Synthesis and antimicrobial activity of small cationic amphipathic aminobenzamide marine natural product mimics and evaluation of relevance against clinical isolates including ESBL-CARBA multi-resistant bacteria

Publication date: Available online 20 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Elizaveta M. Igumnova, Ekaterina Mishchenko, Tor Haug, Hans-Matti Blencke, Johanna U. Ericson Sollid, Elizabeth G. Aarag Fredheim, Silje Lauksund, Klara Stensvåg, Morten B. Strøm
A library of small aminobenzamide derivatives was synthesised to explore a cationic amphipathic motif found in marine natural antimicrobials. The most potent compound E23 displayed minimal inhibitory concentrations (MICs) of 0.5 – 2 μg/ml against several Gram-positive bacterial strains, including methicillin resistant Staphylococcus epidermidis (MRSE).E23 was also potent against 275 clinical isolates including Staphylococcus aureus, Enterococcus spp., Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, as well as methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci (VRE), and ESBL-CARBA multi-resistant Gram-negative bacteria. The study demonstrates how structural motifs found in marine natural antimicrobials can be a valuable source for making novel antimicrobial lead-compounds.

Graphical abstract

http://ift.tt/2d5j5wF

Tyrosyl-DNA phosphodiesterase inhibitors: Progress and potential

Publication date: Available online 20 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Sergey S. Laev, Nariman F. Salakhutdinov, Olga I. Lavrik
DNA topoisomerases are essential during transcription and replication. The therapeutic mechanism of action of topoisomerase inhibitors is enzyme poisoning rather than catalytic inhibition. Tyrosyl-DNA phosphodiesterases 1 or 2 were found as DNA repair enzymes hydrolyzing the covalent bond between the tyrosyl residue of topoisomerases I or II and the 3'- or 5'-phosphate groups in DNA, respectively. Tyrosyl-DNA phosphodiesterase 1 is a key enzyme in DNA repair machinery and a promising target for antitumor and neurodegenerative therapy. Inhibitors of tyrosyl-DNA phosphodiesterase 1 could act synergistically with topoisomerase I inhibitors and thereby potentiate the effects of topoisomerase I poisons. Tyrosyl-DNA phosphodiesterase 2 is an enzyme that specifically repairs DNA damages induced by topoisomerase II poisons and causes resistance to these drugs. Selective inhibition of tyrosyl-DNA phosphodiesterase 2 may be a novel approach to overcome intrinsic or acquired resistance to topoisomerase II-targeted drug therapy. Thus, agents that inhibit tyrosyl-DNA phosphodiesterases 1 and 2 have many applications in biochemical and physiological research and they have the potential to become anticancer and antiviral drugs. The structures, mechanism of action and therapeutic rationale of tyrosyl-DNA phosphodiesterase inhibitors and their development for combinations with topoisomerase inhibitors and DNA damaging agents are discussed.

Graphical abstract

http://ift.tt/2d5j3Vg

A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids and evaluation of their antimycobacterial, anticancer and AchE inhibitory activities

Publication date: Available online 19 September 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Chelliah Bharkavi, Sundaravel Vivek Kumar, Mohamed Ashraf Ali, Hasnah Osman, Shanmugam Muthusubramanian, Subbu Perumal
A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC50 1.07 μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50 < 1.56 μM) and 6l (IC50 = 2.87 μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50 values of 1.10 and 1.16 μmol/L respectively.

Graphical abstract

http://ift.tt/2d5kvHi

Response of wine grape growth, development and the transfer of copper, lead, and cadmium in soil-fruit system to sludge compost amendment

Abstract

Sludge is an organic waste after domestic sewage being treated and contains phytonutrients and organic matter. In this study, recycling of sludge compost (SC) and its compound fertilizer (SCF) to wine grape resulted in improvement in vegetative growth, reproductive development of wine grape, and potential wine quality of grape fruit. The amounts of Cu, Pb, and Cd in grape fruit were significantly higher in response to sludge amendment than in the control, but were all below the permissible limits for agricultural product. The contents of Cu and Pb in sludge-amended soil decreased with increasing soil depth, but Cd content increased with soil depth. Ongoing monitoring of on mobility of Cd downward is proposed with sludge recycling to wine grape soil.

http://ift.tt/2cWdZFq

A modified biotrickling filter for nitrification-denitrification in the treatment of an ammonia-contaminated air stream

Abstract

A conventional biotrickling filter for airborne ammonia nitrification has been modified, by converting the liquid sump into a biological denitrifying reactor. The biotrickling filter achieves an average ammonia removal efficiency of 92.4 %, with an empty bed retention time (EBRT) equal to 36 s and an average ammonia concentration of 54.7 mg Nm⁻³ in the raw air stream. The denitrification reactor converts ammonia into inert gas N₂, in addition to other important advantages connected to the alkaline character of the biochemical pathway of the denitrifying bacteria. Firstly, the trickling water crossing the denitrification reactor underwent a notable pH increase from 7.3 to 8.0 which prevented the acidic inhibition of the nitrifying bacteria due to the buildup of nitric and nitrous acids. Secondly, the pH increase created the ideal conditions for the autotrophic nitrifying bacteria. The tests proved that an ammonia removal efficiency of above 90 % can be achieved with an EBRT greater than 30 s and a volumetric load lower than 200 g NH₃ m⁻³ day⁻¹. The results of the biofilm observation by using a scanning confocal laser microscope are reported together with the identification of degrading bacteria genera in the biotrickling filter. The efficiency of the plant and its excellent operational stability highlight the effectiveness of the synergistic action between the denitrification reactor and the biotrickling filter in removing airborne ammonia.

http://ift.tt/2d59Ufp

Effects of salinity on simultaneous reduction of perchlorate and nitrate in a methane-based membrane biofilm reactor

Abstract

This study builds upon prior work showing that methane (CH₄) could be utilized as the sole electron donor and carbon source in a membrane biofilm reactor (MBfR) for complete perchlorate (ClO₄⁻) and nitrate (NO₃⁻) removal. Here, we further investigated the effects of salinity on the simultaneous removal of the two contaminants in the reactor. By testing ClO₄⁻ and NO₃⁻ at different salinities, we found that the reactor performance was very sensitive to salinity. While 0.2 % salinity did not significantly affect the hydrogen-based MBfR for ClO₄⁻ and NO₃⁻ removals, 1 % salinity completely inhibited ClO₄⁻ reduction and significantly lowered NO₃⁻ reduction in the CH₄-based MBfR. In salinity-free conditions, NO₃⁻ and ClO₄⁻ removal fluxes were 0.171 g N/m²-day and 0.091 g/m²-day, respectively, but NO₃⁻ removal fluxes dropped to 0.0085 g N/m²-day and ClO₄⁻ reduction was completely inhibited when the medium changed to 1 % salinity. Scanning electron microscopy (SEM) showed that the salinity dramatically changed the microbial morphology, which led to the development of wire-like cell structures. Quantitative real-time PCR (qPCR) indicated that the total number of microorganisms and abundances of functional genes significantly declined in the presence of NaCl. The relative abundances of Methylomonas (methanogens) decreased from 31.3 to 5.9 % and Denitratisoma (denitrifiers) decreased from 10.6 to 4.4 % when 1 % salinity was introduced.

http://ift.tt/2cWbXFp