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https://www.readbyqxmd.com/read/28345428/induction-of-t-cell-infiltration-and-programmed-death-ligand-2-expression-by-adeno-associated-virus-in-rhesus-macaque-skeletal-muscle-and-modulation-by-prednisone
#1
Megan L Cramer, Guohong Shao, Louise R Rodino-Klapac, Louis G Chicoine, Paul T Martin
Use of adeno-associated virus (AAV) to transduce genes into skeletal muscles can be associated with T-cell responses to viral capsid and/or to transgenic protein. Intramuscular mononuclear cell infiltrates primarily consisting of CD8+ T cells and also containing FOXP3+ regulatory T cells were present in rhesus macaque skeletal muscle treated with rAAVrh74.MCK.GALGT2 by vascular delivery. Administration of oral prednisone prior to AAV gene delivery and throughout the study reduced such infiltrates by 60% at 24 weeks post-AAV delivery compared to AAV-treated animals not receiving prednisone, regardless of the presence of pre-existing AAV serum antibodies at the time of treatment...
March 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28345023/enhancement-of-psma-directed-car-adoptive-immunotherapy-by-pd-1-pd-l1-blockade
#2
Inna Serganova, Ekaterina Moroz, Ivan Cohen, Maxim Moroz, Mayuresh Mane, Juan Zurita, Larissa Shenker, Vladimir Ponomarev, Ronald Blasberg
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter) were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI). We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA), in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb)...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344882/tumor-pd-l1-expression-is-correlated-with-increased-tils-and-poor-prognosis-in-penile-squamous-cell-carcinoma
#3
Chuangzhong Deng, Zaishang Li, Shengjie Guo, Peng Chen, Xiaofeng Chen, Qianghua Zhou, Jieping Chen, Xingsu Yu, Xiaoliang Wu, Wenjuan Ma, Qiankun Xie, Yunlin Ye, Yonghong Li, Zike Qin, Zhuowei Liu, Ranyi Liu, Zhenfeng Zhang, Kai Yao, Hui Han, Fangjian Zhou
Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumor-infiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344877/impact-of-chemo-radiotherapy-on-immune-cell-composition-and-function-in-cervical-cancer-patients
#4
H van Meir, R A Nout, M J P Welters, N M Loof, M L de Kam, J J van Ham, S Samuels, G G Kenter, A F Cohen, C J M Melief, J Burggraaf, M I E van Poelgeest, S H van der Burg
New treatments based on combinations of standard therapeutic modalities and immunotherapy are of potential use, but require a profound understanding of immune modulatory properties of standard therapies. Here, the impact of standard (chemo)radiotherapy on the immune system of cervical cancer patients was evaluated. Thirty patients with cervical cancer were treated with external beam radiation therapy (EBRT), using conventional three-dimensional or intensity modulated radiation therapy without constraints for bone marrow sparing...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344809/basal-cell-carcinoma-pd-l1-pd-1-checkpoint-expression-and-tumor-regression-after-pd-1-blockade
#5
Evan J Lipson, Mohammed T Lilo, Aleksandra Ogurtsova, Jessica Esandrio, Haiying Xu, Patricia Brothers, Megan Schollenberger, William H Sharfman, Janis M Taube
Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28344662/nivolumab-in-renal-cell-carcinoma-latest-evidence-and-clinical-potential
#6
REVIEW
Camille Mazza, Bernard Escudier, Laurence Albiges
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28343398/an-anti-programmed-death-1-antibody-a%C3%AF-pd-1-fusion-protein-that-self-assembles-into-a-multivalent-and-functional-apd-1-nanoparticle
#7
Peng Zhao, Djordje Atanackovic, Shuyun Dong, Hideo Yagita, Xiao He, Mingnan Chen
Cancer immune checkpoint therapy has achieved remarkable clinical successes in various cancers. However, current immune checkpoint inhibitors block the checkpoint of not only the immune cells that are important to cancer therapy but also the immune cells that are irrelevant to the therapy. Such an indiscriminate blockade limits the efficacy and causes the autoimmune toxicity of the therapy. It might be beneficial to use a carrier to target immune checkpoint inhibitors to cancer-reactive immune cells. Here, we explore a method to load the inhibitors into carriers...
March 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28342871/oxidative-damage-induces-apoptosis-and-promotes-calcification-in-disc-cartilage-endplate-cell-through-ros-mapk-nf-%C3%AE%C2%BAb-pathway-implications-for-disc-degeneration
#8
Yingchao Han, Xinhua Li, Meijun Yan, Mingjie Yang, Shanjin Wang, Jie Pan, Lili Jun, Jun Tan
Cartilage endplate (CEP) cell calcification and apoptosis play a vital role in the intervertebral disc degeneration (IVDD). Oxidative stress is a key factor in inducing programmed cell death and cartilage calcification. However, the cell death and calcification of cartilage endplate cells under oxidative stress have never been described. The present study investigated the apoptosis and calcification in the cartilage endplate cell under oxidative stress induced by H2O2 to understand the underlying mechanism of IVDD...
March 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28342215/efficacy-and-safety-of-nivolumab-in-japanese-patients-with-previously-untreated-advanced-melanoma-a-phase-ii-study
#9
Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Manabu Fujimoto, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami
Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation via overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has demonstrated promising anti-cancer activity in various cancers. We conducted a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma...
March 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28341893/single-prolonged-stress-induced-changes-in-autophagy-related-proteins-beclin-1-lc3-and-p62-in-the-medial-prefrontal-cortex-of-rats-with-post-traumatic-stress-disorder
#10
Shilei Zheng, Fang Han, Yuxiu Shi, Lili Wen, Dan Han
Autophagy, or type II programmed cell death, plays a crucial role in many nervous system diseases. However, few studies have examined the role of autophagy in post-traumatic stress disorder (PTSD), and the mechanisms underlying PTSD are poorly understood. The objective of this research was to explore the expression of three important autophagy-related proteins, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and p62/SQSTM1 (p62), in the medial prefrontal cortex (mPFC) of an animal model of PTSD to identify changes in autophagic activity during PTSD pathogenesis...
March 25, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28341875/pd-l1-overexpression-is-partially-regulated-by-egfr-her2-signaling-and-associated-with-poor-prognosis-in-patients-with-non-small-cell-lung-cancer
#11
Riki Okita, Ai Maeda, Katsuhiko Shimizu, Yuji Nojima, Shinsuke Saisho, Masao Nakata
Immunocheckpoint inhibitors targeting the programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) axis have shown promising results in patients with non-small-cell lung cancer (NSCLC). Recent research has shown that epidermal growth factor receptor (EGFR) signaling affects PD-L1 expression in NSCLC cells; however, the mechanism regulating PD-L1 expression in tumor cells remains unclear. Using immunohistochemistry, we evaluated the impact of expression of PD-L1 and EGF family receptors EGFR and human epidermal growth factor receptor 2 (HER2) in tumor cells from 91 patients with pathological Stage IA-IIIA NSCLC...
March 25, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28340556/innovative-substance-2250-as-a-highly-promising-anti-neoplastic-agent-in-malignant-pancreatic-carcinoma-in-vitro-and-in-vivo
#12
M Buchholz, B Majchrzak-Stiller, S Hahn, D Vangala, R W Pfirrmann, W Uhl, C Braumann, A M Chromik
BACKGROUND: Former studies already revealed the anti-neoplastic properties of the anti-infective agent Taurolidine (TRD) against many tumor species in vitro and in vivo. Its anti-proliferative and cell death inducing capacity is largely due to its main derivative Taurultam (TRLT). In this study it could be demonstrated, that substance 2250 - a newly defined innovative structural analogue of TRLT - exhibits an anti-neoplastic effect on malignant pancreatic carcinoma in vitro and in vivo...
March 24, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28340378/current-fda-approved-treatments-for-non-small-cell-lung-cancer-and-potential-biomarkers-for-its-detection
#13
REVIEW
Karla A Ruiz-Ceja, Yolanda I Chirino
BACKGROUND: Lung cancer is the leading worldwide cancer with almost 1.5 million deaths every year. Some drugs for lung cancer treatment have been available on the market for decades, but novel drugs have emerged promising better outcomes, especially for Non-Small Cell Lung Cancer (NSCLC), which represents 75% of lung cancer cases. However, how much do drugs have evolved for NSCLC treatment? Are they sharing the same mechanism of action? AIM: In this review we analyzed how the approved drugs by Federal Drug Agency for NSCLC have advanced in the last four decades identifying shared mechanism of action of medicines against NSCLC treatment and some of the potential biomarkers for early detection...
March 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28340172/repositioning-disulfiram-as-a-radiosensitizer-against-atypical-teratoid-rhabdoid-tumor
#14
Young Eun Lee, Seung Ah Choi, Pil Ae Kwack, Hak Jae Kim, Il Han Kim, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Sung-Hye Park, Kyung Duk Park, Do Won Hwang, Kyeung Min Joo, Seung-Ki Kim
Background.: Atypical teratoid/rhabdoid tumor (AT/RT) is one of the most common malignant brain tumors in infants. Although cancer stem cells of AT/RT express aldehyde dehydrogenase (ALDH), effective chemotherapies against AT/RT have not been established. Here, we examined radiosensitizing effects of disulfiram (DSF), an irreversible inhibitor of ALDH against AT/RT for a novel therapeutic method. Methods.: Patient-derived primary cultured AT/RT cells (SNU.AT/RT-5 and SNU...
March 17, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28338711/the-effects-of-age-on-crash-risk-associated-with-driver-distraction
#15
Feng Guo, Sheila G Klauer, Youjia Fang, Jonathan M Hankey, Jonathan F Antin, Miguel A Perez, Suzanne E Lee, Thomas A Dingus
Background: Driver distraction is a major contributing factor to crashes, which are the leading cause of death for the US population under 35 years of age. The prevalence of secondary-task engagement and its impacts on distraction and crashes may vary substantially by driver age. Methods: Driving performance and behaviour data were collected continuously using multiple cameras and sensors in situ for 3542 participant drivers recruited for up to 3 years for the Second Strategic Highway Research Program Naturalistic Driving Study...
October 14, 2016: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28338655/evolution-of-caspase-mediated-cell-death-and-differentiation-twins-separated-at-birth
#16
REVIEW
Ryan A V Bell, Lynn A Megeney
The phenotypic and biochemical similarities between caspase-mediated apoptosis and cellular differentiation are striking. They include such diverse phenomenon as mitochondrial membrane perturbations, cytoskeletal rearrangements and DNA fragmentation. The parallels between the two disparate processes suggest some common ancestry and highlight the paradoxical nature of the death-centric view of caspases. That is, what is the driving selective pressure that sustains death-inducing proteins throughout eukaryotic evolution? Plausibly, caspase function may be rooted in a primordial non-death function, such as cell differentiation, and was co-opted for its role in programmed cell death...
March 24, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28337817/the-cytotoxic-effects-of-camptothecin-and-mastoparan-on-the-unicellular-green-alga-chlamydomonas-reinhardtii
#17
Jürgen Voigt, Markus Morawski, Johannes Wöstemeyer
We have recently reported that protease inhibitors affecting the activity of the proteasome cause necrotic cell death in Chlamydomonas reinhardtii instead of inducing apoptosis as shown for some mammalian cell lines. Therefore, we have studied other well-known inducers of apoptosis in mammalian cells for their effects on C. reinhardtii cells. Mastoparan caused rapid cell death without a prominent lag-phase under all growth conditions, whereas the cytotoxic effect of the topoisomerase I inhibitor camptothecin exclusively occured during the cell-division phase...
March 24, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28336131/modulating-the-dna-damage-response-to-improve-treatment-response-in-cervical-cancer
#18
L H Cossar, A G Schache, J M Risk, J J Sacco, N J Jones, R Lord
Cervical cancer is the fourth most common cause of cancer-related death in women worldwide and new therapeutic approaches are needed to improve clinical outcomes for this group of patients. Current treatment protocols for locally advanced and metastatic disease consist of ionising radiation and chemotherapy. Chemoradiation induces cytotoxic levels of DNA double-strand breaks, which activates programmed cell death via the DNA damage response (DDR). Cervical cancers are unique given an almost exclusive association with human papillomavirus (HPV) infection; a potent manipulator of the DDR, with the potential to alter tumour sensitivity to DNA-damaging agents and influence treatment response...
March 20, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28335992/varicella-zoster-virus-vasculopathy-the-expanding-clinical-spectrum-and-pathogenesis
#19
REVIEW
Maria A Nagel, Dallas Jones, Ann Wyborny
Varicella zoster virus (VZV) is a ubiquitous, human alphaherpesvirus that produces varicella on primary infection then becomes latent in ganglionic neurons along the entire neuraxis. In elderly and immunocompromised individuals, VZV reactivates and travels along nerve fibers peripherally resulting in zoster. However, VZV can also spread centrally and infect cerebral and extracranial arteries (VZV vasculopathy) to produce transient ischemic attacks, stroke, aneurysm, sinus thrombosis and giant cell arteritis, as well as granulomatous aortitis...
March 18, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28335643/prospects-and-progress-of-atezolizumab-in-non-small-cell-lung-cancer
#20
Johan Vansteenkiste, Els Wauters, Keunchil Park, Achim Rittmeyer, Alan Sandler, Alexander Spira
Immunotherapy has recently come to the forefront of oncology treatment as a potential means of combating cancer by restoring the body's adaptive cancer-immunity cycle. Atezolizumab is a monoclonal antibody agent that specifically targets programmed death ligand 1 (PD-L1), a key molecule in the cancer-immunity pathway, to block binding to its receptors PD-1 and B7.1. Areas covered: This review covers the role of atezolizumab in the treatment of non-small-cell lung cancer (NSCLC). Several studies have reported promising efficacy in this indication...
March 24, 2017: Expert Opinion on Biological Therapy
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