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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/28527402/a-rare-e13a3-b2a3-bcr-abl1-fusion-transcript-with-normal-karyotype-in-chronic-myeloid-leukemia-the-challenges-in-diagnosis-and-monitoring-minimal-residual-disease-mrd
#2
M-H Duan, H Li, H Cai
Patients with chronic myeloid leukemia (CML) have a t (9;22)(q34;q11.2) or variant translocation that results in a BCR-ABL1 fusion gene. For many years, conventional karyotyping has been used as the standard diagnostic tool for t (9;22) (q34;q11.2). However, it has several limitations that may lead to failure for detecting BCR-ABL1 gene rearrangements in around 5% of all CML patients. Although reverse transcription polymerase chain reaction (RT-PCR) has evolved as a sensitive method for detecting BCR-ABL1 translocation, this method fail to detect certain BCR-ABL1 fusion transcript type, such as e13a3 (also known as b2a3), as a result of many commercially available and laboratory-developed primer sets...
May 12, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28527399/the-effects-of-melamine-with-or-without-cyanuric-acid-on-immune-function-in-ovalbumin-sensitized-mice
#3
Rong H Yin, Qiao Dong, Hua S Li, Jing Yuan, Xi T Li, Rong L Yin, Wen Li, Wen C Wang, Bao S Liu, Xiao H Han, Ren F Wang, Xin Wang, Wen L Bai
Melamine is commonly used in the chemical industry, and it has been found to exist on food processing equipment and utensils. Previous investigations suggested that melamine alone or its combination with cyanuric acid appears to be toxic to immune system in animals. The objective of this study is to investigate the potential effects of melamine with or without cyanuric acid on immune function in ovalbumin- sensitized mice. Our data indicated that melamine-related administration caused a significant decreasing in the content of IL-4 in mice in comparison to negative control group...
May 13, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28527342/relative-efficacy-of-t-cell-stimuli-as-inducers-of-productive-hiv-1-replication-in-latently-infected-cd4-lymphocytes-from-patients-on-suppressive-cart
#4
Nadejda Beliakova-Bethell, Marjan Hezareh, Joseph K Wong, Matthew C Strain, Mary K Lewinski, Douglas D Richman, Celsa A Spina
Quantification of cell-associated replication-competent HIV, in blood samples from patients with undetectable plasma viremia, requires specialized culture conditions that include exogenous pan T cell stimulation. Different research groups have used several stimuli for this purpose; however, the relative efficacies of these T cell stimuli to induce productive HIV replication from latently infected cells ex vivo have not been systematically evaluated. To this end, we compared four commonly used T cell stimuli: 1) irradiated allogeneic cells plus phytohaemagglutinin (PHA); 2) PHA alone; 3) phorbol myristate acetate plus Ionomycin; and 4) immobilized αCD3 plus αCD28 antibodies...
May 17, 2017: Virology
https://www.readbyqxmd.com/read/28527288/-partial-purification-of-peptides-present-in-the-tityus-macrochirus-buthidae-scorpion-venom-and-preliminary-assessment-of-their-cytotoxicity
#5
Clara Andrea Rincón-Cortés, Edgar Antonio Reyes-Montaño, Nohora Angélica Vega-Castro
INTRODUCTION: Scorpion venom contains peptides with neurotoxic action primarily active on ion channels in the nervous system of insects and mammals. They are also characterized as cytolytic and anticancer, biological characteristics that have not yet been reported for the Tityus macrochirus venom. OBJECTIVE: To assess if the total T. macrochirus venom and the fraction of partially purified peptides decrease the viability of various tumor-derived cell lines. MATERIALS AND METHODS: The scorpion venom was collected by electrical stimulation and, subsequently, subjected to chromatography, electrophoresis, and ultrafiltration with Amicon Ultra 0...
June 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28526861/shedding-of-host-autophagic-proteins-from-the-parasitophorous-vacuolar-membrane-of-plasmodium-berghei
#6
Carolina Agop-Nersesian, Mariana De Niz, Livia Niklaus, Monica Prado, Nina Eickel, Volker T Heussler
The hepatic stage of the malaria parasite Plasmodium is accompanied by an autophagy-mediated host response directly targeting the parasitophorous vacuolar membrane (PVM) harbouring the parasite. Removal of the PVM-associated autophagic proteins such as ubiquitin, p62, and LC3 correlates with parasite survival. Yet, it is unclear how Plasmodium avoids the deleterious effects of selective autophagy. Here we show that parasites trap host autophagic factors in the tubovesicular network (TVN), an expansion of the PVM into the host cytoplasm...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526855/gut-homeostasis-and-regulatory-t-cell-induction-depend-on-molecular-chaperone-gp96-in-cd11c-cells
#7
Yunpeng Hua, Yi Yang, Shaoli Sun, Stephen Iwanowycz, Caroline Westwater, Boris Reizis, Zihai Li, Bei Liu
The intestinal immunity and tolerance are orchestrated by both the innate and the adaptive immune system. Intestinal professional antigen presenting cells (pAPCs) recognize and respond to the gut microbiota through multiple pattern-recognition receptors, including TLRs and NLRs. How gut pAPCs maintain mucosal homeostasis remains incompletely understood. Heat shock protein gp96, also known as grp94, is an essential immune chaperone for TLRs. However, the role of gp96 in regulating CD11c(+) APCs in the gut immunity and tolerance is unknown...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526832/identification-of-a-novel-chalcone-derivative-that-inhibits-notch-signaling-in-t-cell-acute-lymphoblastic-leukemia
#8
Mattia Mori, Luca Tottone, Deborah Quaglio, Nadezda Zhdanovskaya, Cinzia Ingallina, Marisa Fusto, Francesca Ghirga, Giovanna Peruzzi, Maria Elisa Crestoni, Fabrizio Simeoni, Francesca Giulimondi, Claudio Talora, Bruno Botta, Isabella Screpanti, Rocco Palermo
Notch signaling is considered a rational target in the therapy of several cancers, particularly those harbouring Notch gain of function mutations, including T-cell acute lymphoblastic leukemia (T-ALL). Although currently available Notch-blocking agents are showing anti-tumor activity in preclinical studies, they are not effective in all the patients and often cause severe side-effects, limiting their widespread therapeutic use. Here, by functional and biological analysis of the most representative molecules of an in house library of natural products, we have designed and synthetized the chalcone-derivative 8 possessing Notch inhibitory activity at low micro molar concentration in T-ALL cell lines...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526760/tissue-resident-t-cells-in-hepatitis-b-a-new-target-for-cure
#9
Fabian J Bolte, Barbara Rehermann
A hallmark of chronic hepatitis B virus (HBV) infection is the functional impairment and depletion of antiviral T cells. In this issue of JEM, Pallett et al. (https://doi.org/10.1084/jem.20162115) identify a reservoir of functional HBV-specific T cells among liver-resident T cells.
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#10
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28526683/autoreactivity-to-sulfatide-by-human-invariant-nkt-cells
#11
Annelein M Stax, Jessica Tuengel, Enrico Girardi, Naoki Kitano, Lenka L Allan, Victor Liu, Dongjun Zheng, William J Panenka, Joren Guillaume, Chi-Huey Wong, Serge van Calenbergh, Dirk M Zajonc, Peter van den Elzen
Invariant NKT (iNKT) cells are innate-like lymphocytes that recognize lipid Ags presented by CD1d. The prototypical Ag, α-galactosylceramide, strongly activates human and mouse iNKT cells, leading to the assumption that iNKT cell physiology in human and mouse is similar. In this article, we report the surprising finding that human, but not mouse, iNKT cells directly recognize myelin-derived sulfatide presented by CD1d. We propose that sulfatide is recognized only by human iNKT cells because of the unique positioning of the 3-O-sulfated β-galactose headgroup...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#12
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526635/arsenic-exposures-alter-clinical-indicators-of-anemia-in-a-male-population-of-smokers-and-non-smokers-in-bangladesh
#13
Faruque Parvez, Sebastian Medina, Regina Santella, Tariqul Islam, Fredine T Lauer, Nur Alam, Mahbubul Eunus, Mizanour Rahman, Pam Factor-Litvak, Habib Ahsan, Joseph Graziano, Ke Jian Liu, Scott W Burchiel
Drinking water arsenic (WAs) exposure has been linked to a number of detrimental health outcomes including anemia, primarily among pregnant women. Little is known about the effects of arsenic (As) on hematological disorders among men. We have examined the role of As exposure on hematological indicators of anemia in a group of men exposed to a wide range of As in their drinking water. We conducted a cross-sectional investigation among 119 healthy men in the Health Effects of As Longitudinal Study (HEALS) cohort, in rural Bangladesh...
May 16, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28526626/longevity-and-healthy-ageing-genes-foxo3a-and-sirt3-serum-protein-marker-and-new-road-map-to-burst-oxidative-stress-by-withania-somnifera
#14
Rashmita Pradhan, Rahul Kumar, Shashank Shekhar, Nitish Rai, Akash Ambashtha, Joyita Banerjee, Mona Pathak, S N Dwivedi, Sharmistha Dey, Aparajit B Dey
BACKGROUND: Ageing process is characterized by a decline in function; different age related diseases and excessive age associated mortality. There has always been a quest for easily accessible biomarkers to monitor and identify the development of age-associated stress for providing new anti-ageing strategies. Forkhead box protein O3A (FOXO3A) and Sirtuin3 (SIRT3) are such potential markers which plays important role in a wide variety of cellular mechanisms and has been proposed to be an ideal candidate to study longevity and are potential candidate for healthy ageing by oxidative burst...
May 16, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28526582/mait-cells-a-tailor-made-mate-in-the-ancient-battle-against-infectious-diseases
#15
REVIEW
Marcela de Lima Moreira, Moriya Tsuji, Alexandra Jane Corbett, Márcio Sobreira Silva Araújo, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho, Vanessa Peruhype-Magalhães, Jordana Grazziela Coelho-Dos-Reis
It has been almost two decades since the discovery of mucosal-associated invariant T (MAIT)-cells. Several advances in the field have been made such as the discovery of the antimicrobial activity of MAIT-cells, the abundance of these cells in human mucosa and in liver and the discovery of ligands able to bind MR1 and activate MAIT-cells. MAIT-cells are a unique subset of innate-like T-cells that express a canonical T-cell receptor with the alpha chain containing hAV7S2 and AJ33 in humans (TCRVα7.2Jα33) and respond to bacterial/fungus vitamin B2 metabolites by an MR1-dependent pathway...
May 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28526573/transcriptomic-variation-of-locally-infected-skin-of-epinephelus-coioides-reveals-the-mucosal-immune-mechanism-against-cryptocaryon-irritans
#16
Yazhou Hu, Anxing Li, Yang Xu, Biao Jiang, Geling Lu, Xiaochun Luo
Fish skin is the largest immunologically active mucosal organ, providing first-line defense against external pathogens. However, the skin-associated immune mechanisms of fish are still unclear. Cryptocaryon irritans is an obligate ectoparasitic ciliated protozoan that infects almost all marine fish, and is believed to be an excellent pathogen model to study fish mucosal immunity. In this study, a de novo transcriptome assembly of Epinephelus coioides skin post C. irritans tail-infection was performed for the first time using the Illumina HiSeq™ 2500 system...
May 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28526557/the-frog-skin-host-defense-peptide-frenatin-2-1s-enhances-recruitment-activation-and-tumoricidal-capacity-of-nk-cells
#17
Jelena M Pantic, Ivan P Jovanovic, Gordana D Radosavljevic, Nevena M Gajovic, Nebojsa N Arsenijevic, J Michael Conlon, Miodrag L Lukic
Frog skin is a source of peptides with various biological properties. Frenatin 2.1S, derived from norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus, exhibits immunostimulatory effects as demonstrated by the promotion of proinflammatory phenotypes of mononuclear cells in mouse peritoneal cavity and spleen. The aim of this study was to identify the populations of host cells sensitive to the action of frenatin 2.1S in vivo and to study its effects on their functional antitumor capacity...
May 16, 2017: Peptides
https://www.readbyqxmd.com/read/28526436/intracranial-il-17a-overexpression-decreases-cerebral-amyloid-angiopathy-by-upregulation-of-abca1-in-an-animal-model-of-alzheimer-s-disease
#18
Junling Yang, Jinghong Kou, Robert Lalonde, Ken-Ichiro Fukuchi
Neuroinflammation is a pervasive feature of Alzheimer's disease (AD) and characterized by activated microglia, increased proinflammatory cytokines and/or infiltrating immune cells. T helper 17 (Th17) cells are found in AD brain parenchyma and interleukin-17A (IL-17A) is identified around deposits of aggregated amyloid β protein (Aβ). However, the role of IL-17A in AD pathogenesis remains elusive. We overexpressed IL-17A in an AD mouse model via recombinant adeno-associated virus serotype 5 (rAAV5)-mediated intracranial gene delivery...
May 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28526413/tcr-crosslinking-promotes-crk-adaptor-protein-binding-to-tyrosine-phosphorylated-cd3%C3%AE-chain
#19
Guangyu Dong, Rachel Kalifa, Pulak Ranjan Nath, Sigal Gelkop, Noah Isakov
T cell antigen receptor (TCR) binding of a peptide antigen presented by antigen-presenting cells (APCs) in the context of surface MHC molecules initiates signaling events that regulate T cell activation, proliferation and differentiation. A key event in the activation process is the phosphorylation of the conserved tyrosine residues within the CD3 chain immunoreceptor tyrosine-based activation motifs (ITAMs), which operate as docking sites for SH2 domain-containing effector proteins. Phosphorylation of the CD3ζ ITAMs renders the CD3 chain capable of binding the ζ-chain associated protein 70 kDa (ZAP70), a protein tyrosine kinase that is essential for T cell activation...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526406/trastuzumab-emtansine-suppresses-the-growth-of-her2-positive-small-cell-lung-cancer-in-preclinical-models
#20
Osamu Morimura, Toshiyuki Minami, Takashi Kijima, Shohei Koyama, Tomoyuki Otsuka, Yuhei Kinehara, Akio Osa, Masayoshi Higashiguchi, Kotaro Miyake, Izumi Nagatomo, Haruhiko Hirata, Kota Iwahori, Takayuki Takimoto, Yoshito Takeda, Hiroshi Kida, Atsushi Kumanogoh
Overcoming chemoresistance is essential for achieving better prognoses in SCLC. Previously, we reported that HER2 is upregulated when HER2-positive SCLC cells acquire chemoresistance. HER2-upregulated cisplatin- or etoposide-resistant SCLC cells were sensitive to trastuzumab-mediated ADCC. However, irinotecan-resistant SCLC cells, such as SBC-3/SN-38, were refractory to trastuzumab despite high HER2 expression. To address this issue, we examined the antitumor efficacy of trastuzumab emtansine (T-DM1) on trastuzumab-resistant HER2-positive SCLC...
May 16, 2017: Biochemical and Biophysical Research Communications
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