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https://www.readbyqxmd.com/read/29786794/protocols-for-studies-on-genetically-engineered-mouse-models-in-prostate-cancer
#1
Chris W D Armstrong, Oksana Lyubomska, Melissa J LaBonte, David J J Waugh
Cancer studies have entered an era that is heavily focused on the contribution of the tumor microenvironment. For this reason, in vivo experimentation in an immunodeficient model system is no longer fit for purpose. As a consequence, numerous genetically engineered mouse models (GEMMs) which self-develop tumors have been developed to allow experiments to be performed in a fully immunocompetent setting. One of the most commonly used technologies is Cre-loxP recombination due to its unique ability to control target gene expression in a specified tissue type...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29784854/molecular-subtype-specific-immunocompetent-models-of-high-grade-urothelial-carcinoma-reveal-differential-neoantigen-expression-and-response-to-immunotherapy
#2
Ryoichi Saito, Christof C Smith, Takanobu Utsumi, Lisa M Bixby, Jordan Kardos, Sara E Wobker, Kyle G Stewart, Shengjie Chai, Ujjawal Manocha, Kevin Matthew Byrd, Jeffrey S Damrauer, Scott E Williams, Benjamin G Vincent, William Y Kim
High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like and basal-like subtypes. We describe here the first subtype-specific murine models of bladder cancer and show that Upk3a-CreERT2; Trp53L/L; PtenL/L; Rosa26LSL-Luc (UPPL: luminal-like) and BBN (basal-like) tumors are more faithful to human bladder cancer than the widely-used MB49 cells. Following engraftment into immunocompetent C57BL/6 mice, BBN tumors were more responsive to PD-1 inhibition than UPPL tumors...
May 21, 2018: Cancer Research
https://www.readbyqxmd.com/read/29783708/following-acute-encephalitis-semliki-forest-virus-is-undetectable-in-the-brain-by-infectivity-assays-but-functional-virus-rna-capable-of-generating-infectious-virus-persists-for-life
#3
Rennos Fragkoudis, Catherine M Dixon-Ballany, Adrian K Zagrajek, Lukasz Kedzierski, John K Fazakerley
Alphaviruses are mosquito-transmitted RNA viruses which generally cause acute disease including mild febrile illness, rash, arthralgia, myalgia and more severely, encephalitis. In the mouse, peripheral infection with Semliki Forest virus (SFV) results in encephalitis. With non-virulent strains, infectious virus is detectable in the brain, by standard infectivity assays, for around ten days. As we have shown previously, in severe combined immunodeficient (SCID) mice, infectious virus is detectable for months in the brain...
May 18, 2018: Viruses
https://www.readbyqxmd.com/read/29782330/a-transgenic-mouse-model-for-hla-b-57-01-linked-abacavir-drug-tolerance-and-reactivity
#4
Marco Cardone, Karla Garcia, Mulualem E Tilahun, Lisa F Boyd, Sintayehu Gebreyohannes, Masahide Yano, Gregory Roderiquez, Adovi D Akue, Leslie Juengst, Elliot Mattson, Suryatheja Ananthula, Kannan Natarajan, Montserrat Puig, David H Margulies, Michael A Norcross
Adverse drug reactions (ADRs) are a major obstacle to drug development, and some of these, including hypersensitivity reactions to the HIV reverse transcriptase inhibitor abacavir (ABC), are associated with HLA alleles, particularly HLA-B*57:01. However, not all HLA-B*57:01+ patients develop ADRs, suggesting that in addition to the HLA genetic risk, other factors may influence the outcome of the response to the drug. To study HLA-linked ADRs in vivo, we generated HLA-B*57:01-Tg mice and show that, although ABC activated Tg mouse CD8+ T cells in vitro in a HLA-B*57:01-dependent manner, the drug was tolerated in vivo...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29780885/a-simple-bioluminescence-imaging-method-for-studying-cancer-cell-growth-and-metastasis-after-subcutaneous-injection-of-lewis-lung-carcinoma-cells-in-syngeneic-c57bl-6-mice
#5
Hong Zhu, Megan E Kauffman, Michael A Trush, Zhenquan Jia, Y Robert Li
In vivo imaging of cancer cell growth and invasion is instrumental in studying cancer cell behavior and in developing effective anticancer agents. In this ROS Protocols article, we report the experimental protocol and steps involving the implantation of luciferase-expressing Lewis lung carcinoma (LLC) cells in normal syngeneic C57BL/6 mice. Using the Berthold NightOwl LB981 in vivo imaging system, we observe the time-dependent growth and invasion of the lung cancer cells following subcutaneous injection of luciferase-expressing LLC cells...
March 2018: Reactive Oxygen Species (Apex, N.C.)
https://www.readbyqxmd.com/read/29780375/effect-of-artinm-on-human-blood-cells-during-infection-with-paracoccidioides-brasiliensis
#6
Luciana P Ruas, Livia M Genaro, Amauri S Justo-Junior, Lilian O Coser, Lívia F de Castro, Plinio Trabasso, Ronei L Mamoni, Maria-Cristina Roque-Barreira, Maria-Heloisa S L Blotta
Infections caused by fungi are prominent in our environment and can be potentially fatal. paracoccidioidomycosis (PCM), caused by fungi of the Paracoccidioides genus, is the most frequent systemic mycosis in Brazil and the main cause of death among immunocompetent individuals. The antifungal therapy for PCM is usually effective but side effects and relapses are often reported. The latter could be avoided with alternative or complementary therapies aimed at boosting the immune response to combat this pathogen...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29779858/-extensive-cutaneous-chromomycosis-efficacy-of-combined-terbinafine-and-cryotherapy
#7
Y Elkhachine, J Elbenaye, M Er-Rami, A Sakkah, A Jakar, M Elhaouri
BACKGROUND: Chromomycosis is a chronic fungal skin infection, mainly affecting the limbs. It is responsible for severe morbidity and its treatment remains long and disappointing. Rarely described in Morocco, we report a new observation that has evolved very well under treatment combining terbinafine and cryotherapy over a short duration. CASE REPORT: A 56-year-old patient, immunocompetent, had a pustular and crusty placard on both forearms that had evolved for a year...
May 17, 2018: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/29779479/optimizing-antitumor-efficacy-and-adverse-effects-of-pegylated-liposomal-doxorubicin-by-scheduled-plasmapheresis-impact-of-timing-and-dosing
#8
Romeo Ngoune, Christine Contini, Michael Marcus Hoffmann, Dominik Elverfeldt, Karl Winkler, Gerhard Putz
BACKGROUND: Nanoscale drug delivery systems accumulate in solid tumors preferentially by the enhanced permeation and retention effect (EPR-effect). Nevertheless, only a miniscule fraction of a given dosage reaches the tumor, while >90% of the given drug ends up in otherwise healthy tissues, leading to the severe toxic reactions observed during chemotherapy. Once accumulation in tumor has reached its maximum, extracorporeal elimination of circulating nanoparticles by plasmapheresis can diminish toxicities...
May 18, 2018: Current Drug Delivery
https://www.readbyqxmd.com/read/29777108/factor-xiiia-expressing-inflammatory-monocytes-promote-lung-squamous-cancer-through-fibrin-cross-linking
#9
Alessandro Porrello, Patrick L Leslie, Emily B Harrison, Balachandra K Gorentla, Sravya Kattula, Subrata K Ghosh, Salma H Azam, Alisha Holtzhausen, Yvonne L Chao, Michele C Hayward, Trent A Waugh, Sanggyu Bae, Virginia Godfrey, Scott H Randell, Cecilia Oderup, Liza Makowski, Jared Weiss, Matthew D Wilkerson, D Neil Hayes, H Shelton Earp, Albert S Baldwin, Alisa S Wolberg, Chad V Pecot
Lung cancer is the leading cause of cancer-related deaths worldwide, and lung squamous carcinomas (LUSC) represent about 30% of cases. Molecular aberrations in lung adenocarcinomas have allowed for effective targeted treatments, but corresponding therapeutic advances in LUSC have not materialized. However, immune checkpoint inhibitors in sub-populations of LUSC patients have led to exciting responses. Using computational analyses of The Cancer Genome Atlas, we identified a subset of LUSC tumors characterized by dense infiltration of inflammatory monocytes (IMs) and poor survival...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29776955/high-fat-diet-induced-inflammation-accelerates-prostate-cancer-growth-via-il6-signaling
#10
Takuji Hayashi, Kazutoshi Fujita, Satoshi Nojima, Yujiro Hayashi, Kosuke Nakano, Yu Ishizuya, Cong Wang, Yoshiyuki Yamamoto, Toshiro Kinouchi, Kyosuke Matsuzaki, Kentaro Jingushi, Taigo Kato, Atsunari Kawashima, Akira Nagahara, Takeshi Ujike, Motohide Uemura, Maria Del Carmen Rodriguez Pena, Jennifer B Gordetsky, Eiichi Morii, Kazutake Tsujikawa, George J Netto, Norio Nonomura
OBJECTIVE: High-fat diet (HFD) could induce prostate cancer progression. The aim of this study is to identify mechanisms of HFD-induced prostate cancer progression, focusing on inflammation. MATERIALS AND METHODS: We administered HFD and celecoxib to autochthonous immunocompetent Pb-Cre+; Pten(fl/fl) model mice for prostate cancer. Tumor growth was evaluated by tumor weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29770133/peripheral-blood-stem-cell-mobilization-in-healthy-donors-by-granulocyte-colony-stimulating-factor-causes-preferential-mobilization-of-lymphocyte-subsets
#11
Guro Kristin Melve, Elisabeth Ersvaer, Geir Egil Eide, Einar K Kristoffersen, Øystein Bruserud
Background: Allogeneic hematopoietic stem cell transplantation is associated with a high risk of immune-mediated post-transplant complications. Graft depletion of immunocompetent cell subsets is regarded as a possible strategy to reduce this risk without reducing antileukemic immune reactivity. Study design and methods: We investigated the effect of hematopoietic stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) on peripheral blood and stem cell graft levels of various T, B, and NK cell subsets in healthy donors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29769782/graft-versus-host-disease-presenting-as-fibrosing-alopecia-in-a-pattern-distribution-a-model-for-pathophysiological-understanding-of-cicatricial-pattern-hair-loss
#12
Hudson Dutra Rezende, Maria Fernanda Reis Gavazzoni Dias, Ralph Michel Trüeb
A case of cutaneous graft versus host disease (GvHD) presenting as fibrosing alopecia in a pattern distribution (FAPD) is discussed, possibly providing a mechanistic model for a better understanding of the pathogenic events underlying cicatricial pattern hair loss. The implication of a follicular inflammation and fibrosis associated with patterned hair loss has emerged from several independent studies. Eventually, Zinkernagel and Trüeb reported a peculiar type of cicatricial pattern hair loss with histopathological features consistent with lichen planopilaris (LPP) associated with androgenetic alopecia (AGA)...
March 2018: International Journal of Trichology
https://www.readbyqxmd.com/read/29769087/replacement-of-feline-foamy-virus-bet-by-feline-immunodeficiency-virus-vif-yields-replicative-virus-with-novel-vaccine-candidate-potential
#13
Carmen Ledesma-Feliciano, Sarah Hagen, Ryan Troyer, Xin Zheng, Esther Musselman, Dragana Slavkovic Lukic, Ann-Mareen Franke, Daniel Maeda, Jörg Zielonka, Carsten Münk, Guochao Wei, Sue VandeWoude, Martin Löchelt
BACKGROUND: Hosts are able to restrict viral replication to contain virus spread before adaptive immunity is fully initiated. Many viruses have acquired genes directly counteracting intrinsic restriction mechanisms. This phenomenon has led to a co-evolutionary signature for both the virus and host which often provides a barrier against interspecies transmission events. Through different mechanisms of action, but with similar consequences, spumaviral feline foamy virus (FFV) Bet and lentiviral feline immunodeficiency virus (FIV) Vif counteract feline APOBEC3 (feA3) restriction factors that lead to hypermutation and degradation of retroviral DNA genomes...
May 16, 2018: Retrovirology
https://www.readbyqxmd.com/read/29766028/a-non-integrating-lentiviral-approach-overcomes-cas9-induced-immune-rejection-to-establish-an-immunocompetent-metastatic-renal-cancer-model
#14
Junhui Hu, Shiruyeh Schokrpur, Maani Archang, Kip Hermann, Allison C Sharrow, Prateek Khanna, Jesse Novak, Sabina Signoretti, Rupal S Bhatt, Beatrice S Knudsen, Hua Xu, Lily Wu
The CRISPR-based technology has revolutionized genome editing in recent years. This technique allows for gene knockout and evaluation of function in cell lines in a manner that is far easier and more accessible than anything previously available. Unfortunately, the ability to extend these studies to in vivo syngeneic murine cell line implantation is limited by an immune response against cells transduced to stably express Cas9. In this study, we demonstrate that a non-integrating lentiviral vector approach can overcome this immune rejection and allow for the growth of transduced cells in an immunocompetent host...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29765411/skin-derived-stem-cells-for-wound-treatment-using-cultured-epidermal-autografts-clinical-applications-and-challenges
#15
REVIEW
Inga Brockmann, Juliet Ehrenpfordt, Tabea Sturmheit, Matthias Brandenburger, Charli Kruse, Marietta Zille, Dorothee Rose, Johannes Boltze
The human skin fulfills important barrier, sensory, and immune functions-all of which contribute significantly to health and organism integrity. Widespread skin damage requires immediate treatment and coverage because massive skin loss fosters the invasion of pathogens, causes critical fluid loss, and may ultimately lead to death. Since the skin is a highly immunocompetent organ, autologous transplants are the only viable approach to permanently close a widespread skin wound. Despite the development of tissue-saving autologous transplantation techniques such as mesh and Meek grafts, treatment options for extensive skin damage remain severely limited...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29761734/functional-effects-of-trka-inhibition-on-system-x-c-mediated-glutamate-release-and-cancer-induced-bone-pain
#16
Tanya Miladinovic, Robert G Ungard, Katja Linher-Melville, Snezana Popovic, Gurmit Singh
Breast cancer cells release the signalling molecule glutamate via the system xC - antiporter, which is upregulated to exchange extracellular cystine for intracellular glutamate to protect against oxidative stress. Here, we demonstrate that this antiporter is functionally influenced by the actions of the neurotrophin nerve growth factor on its cognate receptor tyrosine kinase, TrkA, and that inhibiting this complex may reduce cancer-induced bone pain via its downstream actions on xCT, the functional subunit of system xC - ...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29755958/gut-microbiota-contributes-to-resistance-against-pneumococcal-pneumonia-in-immunodeficient-rag-mice
#17
Krysta M Felix, Ivan A Jaimez, Thuy-Vi V Nguyen, Heqing Ma, Walid A Raslan, Christina N Klinger, Kristian P Doyle, Hsin-Jung J Wu
Streptococcus pneumoniae causes infection-related mortality worldwide. Immunocompromised individuals, including young children, the elderly, and those with immunodeficiency, are especially vulnerable, yet little is known regarding S. pneumoniae- related pathogenesis and protection in immunocompromised hosts. Recently, strong interest has emerged in the gut microbiota's impact on lung diseases, or the "gut-lung axis." However, the mechanisms of gut microbiota protection against gut-distal lung diseases like pneumonia remain unclear...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29755280/-blastomyces-species-and-orbital-apex-syndrome-unsuspected-co-infection
#18
Janice R Safneck, Sherry Krawitz
Blastomyces species are thermally dimorphic fungi existing as yeast in tissue. We report an initially immunocompetent patient with orbital apex syndrome (OAS) whose presentation suggested giant cell arteritis. Subsequently, metastatic carcinoma was entertained as a cause of OAS until bronchoscopy yielded Blastomyces species. The patient rapidly succumbed with multiorgan failure despite Amphotericin B administration. At post-mortem, Blastomyces co-infection with fungal hyphae in keeping with Aspergillus species was found in cavernous sinus and in infarcted optic nerve...
January 2018: Saudi Journal of Ophthalmology: Official Journal of the Saudi Ophthalmological Society
https://www.readbyqxmd.com/read/29754134/surprising-pathological-and-clinical-manifestations-of-miliary-tuberculosis
#19
Kamonkiat Wirunsawanya, Dennis Thomas Bolger
We report a surprising pathological finding of miliary tuberculosis (TB) in a 49-year-old Chuukese, immunocompetent woman who was initially admitted to the hospital for a 1-month duration of chronic abdominal pain and intermittent fevers. Her clinical symptoms did not improve despite treatment with vancomycin and piperacillin-tazobactam. Based on the primary abdominal CT findings suggesting advanced ovarian cancer with omental metastatic disease, further workup with omental core biopsy was performed and demonstrated acute neutrophilic necrosis without malignant cells or granulomata...
May 12, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29750890/impact-of-age-on-disease-progression-and-microenvironment-in-oral-cancer
#20
V K Vincent-Chong, H DeJong, L J Rich, A Patti, M Merzianu, P A Hershberger, M Seshadri
Despite the recognized link between aging and cancer, most preclinical studies in experimental tumor models are conducted with 6- to 8-wk-old rodents. The goal of the present study was to examine the impact of age on tumor incidence, growth, and microenvironmental characteristics in mouse models of head and neck squamous cell carcinoma (HNSCC). Experimental studies were conducted with the 4-nitroquinoline-oxide (4NQO) oral carcinogenesis model and orthotopic FaDu HNSCC xenografts, established in young (7 to 12 wk of age) and old (65 to 70 wk of age) female C57BL/6 mice ( n = 44; 4NQO model) and severe combined immunodeficient mice ( n = 13; HNSCC xenografts)...
May 1, 2018: Journal of Dental Research
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