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https://www.readbyqxmd.com/read/28527407/mechanisms-of-resistance-to-systemic-therapy-in-metastatic-castration-resistant-prostate-cancer
#1
REVIEW
Giuseppe Galletti, Benjamin I Leach, Linda Lam, Scott T Tagawa
Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgen receptor (AR)-targeted therapies (enzalutamide, abiraterone), a radioisotope (radium-223) and a cancer vaccine (sipuleucel-T). However, the optimal treatment sequencing pathway is unknown, and this problem is exacerbated by the issues of primary and acquired resistance. This review focuses on mechanisms of resistance to AR-targeted therapies and taxane-based chemotherapy...
May 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28527341/unravelling-respiratory-syncytial-virus-outbreaks-in-buenos-aires-argentina-molecular-basis-of-the-spatio-temporal-transmission
#2
Gabriel Lihue Rojo, Stephanie Goya, Mariana Orellana, Andrea Sancilio, Alberto Rodriguez Perez, César Montali, Carolina García, Lilian Sosa, Alejandra Musto, Daniela Alvarez, Alejandro Castello, Mariana Viegas
Respiratory syncytial virus (RSV) is the main viral cause of hospitalization due to acute lower respiratory tract infections in infants worldwide. Several vaccines against RSV are under research and development, which are about to be approved. We evaluated transmission patterns in different settings to determine age-specific vaccination targets from a viral perspective. We sequenced the G glycoprotein's ectodomain of a constant clinical sampling between two epidemic outbreaks in a limited geographical region and performed phylogeographic analyses...
May 17, 2017: Virology
https://www.readbyqxmd.com/read/28527094/circulating-tumor-dna-measurement-by-picoliter-droplet-based-digital-pcr-and-vemurafenib-plasma-concentrations-in-patients-with-advanced-braf-mutated-melanoma
#3
Fanny Garlan, Benoit Blanchet, Nora Kramkimel, Alicja Puszkiel, Jean-Louis Golmard, Gaelle Noe, Nicolas Dupin, Pierre Laurent-Puig, Michel Vidal, Valerie Taly, Audrey Thomas-Schoemann
BACKGROUND: Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis. OBJECTIVE: We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients. PATIENTS AND METHODS: Eleven patients treated with single-agent vemurafenib for advanced BRAF V600-mutant melanoma were analyzed in an exploratory monocentric study...
May 19, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28526922/advances-in-systemic-therapy-for-metastatic-breast-cancer-future-perspectives
#4
REVIEW
S P Corona, N Sobhani, A Ianza, G Roviello, G Mustacchi, M Bortul, F Zanconati, D Generali
Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease...
July 2017: Medical Oncology
https://www.readbyqxmd.com/read/28526820/multi-label-learning-for-predicting-the-activities-of-antimicrobial-peptides
#5
Pu Wang, Ruiquan Ge, Liming Liu, Xuan Xiao, Ye Li, Yunpeng Cai
Antimicrobial peptides (AMPs) are peptide antibiotics with a broad spectrum of antimicrobial activities. Activity prediction of AMPs from their amino acid sequences is of great therapeutic importance but imposes challenges on prediction methods due to label interactions. In this paper we propose a novel multi-label learning model to address this problem. A weighted K-nearest neighbor classifier is adopted for efficient representation learning of the sequence data. A multiple linear regression model is then employed to learn a mapping from the classifier score vectors to the target labels, with label correlations considered...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526816/delineation-of-b-cell-epitopes-of-salmonella-enterica-serovar-typhi-hemolysin-e-potential-antibody-therapeutic-target
#6
Chai Fung Chin, Jing Yi Lai, Yee Siew Choong, Amy Amilda Anthony, Asma Ismail, Theam Soon Lim
Hemolysin E (HlyE) is an immunogenic novel pore-forming toxin involved in the pathogenesis of typhoid fever. Thus, mapping of B-cell epitopes of Salmonella enterica serovar Typhi (S. Typhi) is critical to identify key immunogenic regions of HlyE. A random 20-mer peptide library was used for biopanning with enriched anti-HlyE polyclonal antibodies from typhoid patient sera. Bioinformatic tools were used to refine, analyze and map the enriched peptide sequences against the protein to identify the epitopes. The analysis identified both linear and conformational epitopes on the HlyE protein...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526814/kras-and-gnas-co-mutation-in-metastatic-low-grade-appendiceal-mucinous-neoplasm-lamn-to-the-ovaries-a-practical-role-for-next-generation-sequencing
#7
Daniel R Matson, Jin Xu, Laura Huffman, Lisa Barroilhet, Molly Accola, William M Rehrauer, Paul Weisman
BACKGROUND Low-grade appendiceal mucinous neoplasms (LAMNs) are cytologically low-grade tumors of the appendix and are a frequent cause of pseudomyxoma peritonei. They can become a diagnostic challenge when they metastasize to the ovaries, where they may mimic primary ovarian mucinous tumors. CASE REPORT We report the case of a patient with very large bilateral ovarian mucinous tumors and a concurrent minute LAMN incidentally discovered in a grossly normal appendix. A primary ovarian tumor was suspected, but histological analysis of the ovaries suggested an appendiceal origin...
May 20, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28526796/sulfide-induced-dissimilatory-nitrate-reduction-to-ammonium-supports-anammox-in-an-open-water-unit-process-wetland
#8
Zackary L Jones, Justin T Jasper, David L Sedlak, Jonathan O Sharp
Open-water unit process wetlands host a benthic diatomaceous and bacterial assemblage capable of nitrate removal from treated municipal wastewater with unexpected contributions from anammox processes. In exploring mechanistic drivers of anammox, 16S rRNA gene sequencing profiles of the biomat revealed significant microbial community shifts along the flow path and with depth. Notably there was an increasing abundance of sulfate reducers (Desulfococcus and other Deltaproteobacteria) and anammox microorganisms (Brocadiaceae) with depth...
May 19, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28526795/exploring-a-possible-link-between-the-intestinal-microbiota-and-feed-efficiency-in-pigs
#9
Ursula M McCormack, Tânia Curião, Stefan G Buzoianu, Maria L Prieto, Tomas Ryan, Patrick Varley, Fiona Crispie, Elizabeth Magowan, Barbara U Metzler-Zebeli, Donagh Berry, Orla O'Sullivan, Paul D Cotter, Gillian E Gardiner, Peadar G Lawlor
Feed efficiency (FE) is critical in pig production for both economic and environmental reasons. As the intestinal microbiota plays an important role in energy harvest, it is likely to influence FE. Our aim was therefore to characterize the intestinal microbiota of pigs ranked as low, medium and high residual feed intake (RFI; a metric for FE), where genetic, nutritional and management effects were minimized, in order to explore a possible link between the intestinal microbiota and FE. Eighty one pigs were ranked on RFI between weaning and day 126 post-weaning, and 32 were selected as the extremes in RFI (12 low, 10 medium, 10 high)...
May 19, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28526743/systematic-identification-of-functional-residues-of-artemisia-annua-amorpha-4-11-diene-synthase
#10
Xin Fang, Jian-Xu Li, Jin-Quan Huang, You-Li Xiao, Peng Zhang, Xiao-Ya Chen
Terpene synthases (TPSs) are responsible for the extremely diversified and complex structure of terpenoids. Amorpha-4,11-diene synthase (ADS) has a high (90%) fidelity in generating the sesquiterpene precursor for biosynthesis of artemisinin, an antimalarial drug, however, little is known about how active site residues of ADS involved in the carbocation rearrangement and cyclization reactions. Here, we identify seven residues that are key to most of the catalytic steps in ADS. By structural modeling and amino acid sequence alignments of ADS with two functionally relevant sesquiterpene synthases from Artemisia annua, we performed site-directed mutagenesis and found that a single substitution, T296V, impaired the ring closure activity almost completely, and tetra-substitutions (L374Y/L404V/L405I/G439S) led to an enzyme generating 80% monocyclic bisabolyl-type sesquiterpenes, whereas a double mutant (T399L/T447G) showed compromised activity in regioselective deprotonation to yield 34...
May 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28526730/a-targeted-capture-linkage-map-anchors-the-genome-of-the-schistosomiasis-vector-snail-biomphalaria-glabrata
#11
Jacob A Tennessen, Stephanie R Bollmann, Michael S Blouin
The aquatic planorbid snail Biomphalaria glabrate is one of the most intensively-studied mollusks due to its role in the transmission of schistosomiasis. Its 916 Mb genome has recently been sequenced and annotated, but it remains poorly assembled. Here we used targeted capture markers to map over 10,000 B. glabrate scaffolds in a linkage cross of 94 F1 offspring, generating 24 linkage groups. We added additional scaffolds to these linkage groups based on linkage disequilibrium analysis of targeted capture and whole-genome sequences of 96 unrelated snails...
May 19, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28526728/genetic-subtraction-profiling-identifies-candidate-mirnas-involved-in-rice-female-gametophyte-abortion
#12
Liyu Yang, Ya Wu, Wenliang Wang, Bigang Mao, Bingran Zhao, Jianbo Wang
Female gametophyte is an important participant in sexual reproduction of plants. The molecular mechanism of its development has received much attention in recent years. As important regulators of gene expression, miRNAs have been certified to play a significant role in many biological processes of plants including sexual reproduction. In this study, to investigate the potential regulatory effects of miRNAs on rice female gametophytes abortion, we used the high-throughput sequencing method to compare the miRNA transcriptome in ovules of a high frequency female-sterile line (fsv1) and a rice wild-type line (Gui 99) during ovule development...
May 19, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28526529/adding-biological-meaning-to-human-protein-protein-interactions-identified-by-yeast-two-hybrid-screenings-a-guide-through-bioinformatics-tools
#13
Juliana Felgueiras, Joana Vieira Silva, Margarida Fardilha
"A man is known by the company he keeps" is a popular expression that perfectly fits proteins. A common approach to characterize the function of a target protein is to identify its interacting partners and thus infer its roles based on the known functions of the interactors. Protein-protein interaction networks (PPINs) have been created for several organisms, including humans, primarily as results of high-throughput screenings, such as yeast two-hybrid (Y2H). Their unequivocal use to understand events underlying human pathophysiology is promising in identifying genes and proteins associated with diseases...
May 16, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28526096/pvgama-reticulocyte-binding-activity-predicting-conserved-functional-regions-by-natural-selection-analysis
#14
Luis A Baquero, Darwin A Moreno-Pérez, Diego Garzón-Ospina, Johanna Forero-Rodríguez, Heidy D Ortiz-Suárez, Manuel A Patarroyo
BACKGROUND: Adhesin proteins are used by Plasmodium parasites to bind and invade target cells. Hence, characterising molecules that participate in reticulocyte interaction is key to understanding the molecular basis of Plasmodium vivax invasion. This study focused on predicting functionally restricted regions of the P. vivax GPI-anchored micronemal antigen (PvGAMA) and characterising their reticulocyte binding activity. RESULTS: The pvgama gene was initially found in P...
May 19, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28526081/comprehensive-detection-of-germline-variants-by-msk-impact-a-clinical-diagnostic-platform-for-solid-tumor-molecular-oncology-and-concurrent-cancer-predisposition-testing
#15
Donavan T Cheng, Meera Prasad, Yvonne Chekaluk, Ryma Benayed, Justyna Sadowska, Ahmet Zehir, Aijazuddin Syed, Yan Elsa Wang, Joshua Somar, Yirong Li, Zarina Yelskaya, Donna Wong, Mark E Robson, Kenneth Offit, Michael F Berger, Khedoudja Nafa, Marc Ladanyi, Liying Zhang
BACKGROUND: The growing number of Next Generation Sequencing (NGS) tests is transforming the routine clinical diagnosis of hereditary cancers. Identifying whether a cancer is the result of an underlying disease-causing mutation in a cancer predisposition gene is not only diagnostic for a cancer predisposition syndrome, but also has significant clinical implications in the clinical management of patients and their families. METHODS: Here, we evaluated the performance of MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) in detecting genetic alterations in 76 genes implicated in cancer predisposition syndromes...
May 19, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28525982/blood-meal-induced-regulation-of-the-chemosensory-gene-repertoire-in-the-southern-house-mosquito
#16
Tanvi Taparia, Rickard Ignell, Sharon Rose Hill
BACKGROUND: The southern house mosquito, Culex quinquefasciatus, is one of the most prevalent vectors of lymphatic filariasis and flavivirus-induced encephalitis. Its vectorial capacity is directly affected by its reproductive feeding behaviors, such as host seeking, blood feeding, resting, and egg laying. In mosquitoes, these gonotrophic behaviors are odor-mediated and regulated following blood feeding. Immediately after a blood meal, female mosquitoes show reduced olfactory responsiveness and flight activity, as they enter a resting state...
May 19, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28525976/the-adaptation-of-colorectal-cancer-cells-when-forming-metastases-in-the-liver-expression-of-associated-genes-and-pathways-in-a-mouse-model
#17
Derya Bocuk, Alexander Wolff, Petra Krause, Gabriela Salinas, Annalen Bleckmann, Christina Hackl, Tim Beissbarth, Sarah Koenig
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related death in men and women. Systemic disease with metastatic spread to distant sites such as the liver reduces the survival rate considerably. The aim of this study was to investigate the changes in gene expression that occur on invasion and expansion of CRC cells when forming metastases in the liver. METHODS: The livers of syngeneic C57BL/6NCrl mice were inoculated with 1 million CRC cells (CMT-93) via the portal vein, leading to the stable formation of metastases within 4 weeks...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28525954/construction-of-various-%C3%AE-34-5-deleted-fluorescent-expressing-oncolytic-herpes-simplex-type-1-ohsv-for-generation-and-isolation-of-hsv-based-vectors
#18
REVIEW
Shahriyar Abdoli, Farzin Roohvand, Ladan Teimoori-Toolabi, Mohammad Ali Shokrgozar, Mina Bahrololoumi, Kayhan Azadmanesh
Background: Oncolytic herpes simplex virus (oHSV)-based vectors lacking γ34.5 gene, are considered as ideal templates to construct efficient vectors for (targeted) cancer gene therapy. Herein, we reported the construction of three single/dually-flourescence labeled and γ34.5-deleted, recombinant HSV-1 vectors for rapid generation and easy selection/isolation of different HSV-Based vectors. Methods: Generation of recombinant viruses was performed with conventional homologous recombination methods using green fluorescent protein (GFP) and BleCherry harboring shuttle vectors...
July 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28525837/differentially-expressed-jak-stat-signaling-pathway-genes-and-target-micrornas-in-the-spleen-of-necrotic-enteritis-afflicted-chicken-lines
#19
Anh Duc Truong, Deivendran Rengaraj, Yeojin Hong, Cong Thanh Hoang, Yeong Ho Hong, Hyun S Lillehoj
The JAK signal transducer and STAT signaling pathway is an important regulator of cell proliferation, differentiation, survival, motility, apoptosis, immune response, and development. In this study, we used RNA-Sequencing, qRT-PCR, and bioinformatics tools to investigate the differential expression of JAK-STAT pathway genes, their interactions, and regulators in the spleen of two genetically disparate chicken lines (Marek's disease-resistant line 6.3 and MD-susceptible line 7.2) induced necrotic enteritis (NE) disease by co-infection with Eimeria maxima and Clostridium perfringens...
May 13, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28525638/glucokinase-gene-may-be-a-more-suitable-target-than-the-insulin-gene-for-detection-of-beta-cell-death
#20
J Sklenarova, L Petruzelkova, S Kolouskova, J Lebl, Z Sumnik, O Cinek
Detection and quantification of unmethylated circulating insulin (INS) DNA presumably released from beta cells has been previously used for assessing their destruction. As the targets within the INS gene suffer from suboptimal specificity, we sought to improve the assay parameters by using the glucokinase gene (GCK) tissue-specific pancreatic promoter.The amount of methylated and unmethylated GCK DNA was measured using a droplet PCR assay, and compared with the previously published INS-targeted assay. The method was tested using synthetic target sequences and DNA from pancreatic islets, blood, brain, kidney, large intestine, liver, lung, small intestine and stomach...
May 18, 2017: Endocrinology
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