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https://www.readbyqxmd.com/read/28637250/use-of-spytag-spycatcher-to-construct-bispecific-antibodies-that-target-two-epitopes-of-a-single-antigen
#1
Kyohei Yumura, Hiroki Akiba, Satoru Nagatoishi, Osamu Kusano-Arai, Hiroko Iwanari, Takao Hamakubo, Kouhei Tsumoto
Bispecific antibody targeting of two different antigens is promising, but when fragment-based antibodies are used, homogeneous production is difficult. To overcome this difficulty, we developed a method using the SpyTag/SpyCatcher system in which a covalent bond is formed between the two polypeptides. Using this method, we constructed a bispecific antibody that simultaneously interacted with two different epitopes of ROBO1, a membrane protein associated with cancer progression. A bispecific tetravalent antibody with an additional functional moiety was also constructed by using a dimeric biotin-binding protein...
June 16, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28637240/tfeb-activation-restores-migration-ability-to-tsc1-deficient-adult-neural-stem-progenitor-cells
#2
Alessandro Magini, Alice Polchi, Danila Di Meo, Giuseppina Mariucci, Krizia Sagini, Federico De Marco, Tommaso Cassano, Stefano Giovagnoli, Diego Dolcetta, Carla Emiliani
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). mTOR inhibitors are now considered the treatment of choice for TSC disease. A major pathological feature of TSC is the development of subependymal giant cell astrocytomas (SEGAs) in the brain. Nowadays, it is thought that SEGAs could be a consequence of aberrant aggregation and migration of neural stem/progenitor cells (NSPCs)...
June 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28637024/tumor-location-impacts-immune-response-in-mouse-models-of-colon-cancer
#3
Xianda Zhao, Lihua Li, Timothy K Starr, Subbaya Subramanian
Existing preclinical models of human colorectal cancer (CRC) that rely on syngeneic subcutaneous grafts are problematic, because of increasing evidence that the immune microenvironment in subcutaneous tissue is significantly different from the gastrointestinal tract. Similarly, existing orthotopic models that use a laparotomy for establishing grafts are also problematic, because the surgical procedure results in extensive inflammation, thereby creating a nonphysiologic tumor microenvironment. To facilitate the bench-to-bedside translation of CRC immunotherapy strategies, we developed a novel orthotopic model in mice that uses endoscopy-guided microinjection of syngeneic cancer cells...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637021/dectin-1-signaling-inhibits-osteoclastogenesis-via-il-33-induced-inhibition-of-nfatc1
#4
Xiaoqing Zhu, Yinghua Zhao, Yuxue Jiang, Tianxue Qin, Jintong Chen, Xiao Chu, Qing Yi, Sujun Gao, Siqing Wang
Abnormal osteoclast activation contributes to osteolytic bone diseases (OBDs). It was reported that curdlan, an agonist of dectin-1, inhibits osteoclastogenesis. However, the underlying mechanisms are not fully elucidated. In this study, we found that curdlan potently inhibited RANKL-induced osteoclast differentiation and the resultant bone resorption. Curdlan inhibited the expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), the key transcriptional factor for osteoclastogenesis. Notably, dectin-1 activation increased the expression of MafB, an inhibitor of NFATc1, and IL-33 in osteoclast precursors...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637019/clinicopathological-characteristics-of-ros1-and-ret-rearranged-nsclc-in-caucasian-patients-data-from-a-cohort-of-713-non-squamous-nsclc-lacking-kras-egfr-her2-braf-pik3ca-alk-alterations
#5
Frédéric Dugay, Francisco Llamas-Gutierrez, Marjory Gournay, Sarah Medane, François Mazet, Dan Christian Chiforeanu, Emmanuelle Becker, Régine Lamy, Hervé Léna, Nathalie Rioux-Leclercq, Marc-Antoine Belaud-Rotureau, Florian Cabillic
Targeted therapies have substantially changed the management of non-small cell lung cancer (NSCLC) patients with driver oncogenes. Given the high frequency, EGFR and ALK aberrations were the first to be detected and paved the way for tyrosine kinase inhibitor (TKI) treatments. Other kinases such as ROS1 and more recently RET have emerged as promising targets, and ROS1 and RET TKIs are already available for precision medicine.We screened a large cohort of 713 Caucasian non-squamous NSCLC patients lacking EGFR/KRAS/BRAF/HER2/PI3KCA/ALK aberrations for ROS1 and RET rearrangements using fluorescence in situ hybridization to determine the frequency and clinicopathological characteristics of ROS1- and RET-positive patients...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637018/the-efficacy-of-anti-pd-1-pd-l1-therapy-and-its-comparison-with-egfr-tkis-for-advanced-non-small-cell-lung-cancer
#6
REVIEW
Zhixin Sheng, Xu Zhu, Yanhua Sun, Yanxia Zhang
PURPOSE: To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC). METHODS: The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in previously treated patients with advanced NSCLC. RESULTS: Finally, we identified 14 prospective published reports including four trials of atezolizumab covering 542 subjects, three trials of pembrolizumab covering 1566 subjects, seven trials of nivolumab covering 1678 subjects...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637013/akt-can-modulate-the-in-vitro-response-of-hnscc-cells-to-irreversible-egfr-inhibitors
#7
Renato José Silva-Oliveira, Matias Melendez, Olga Martinho, Maicon F Zanon, Luciano de Souza Viana, André Lopes Carvalho, Rui Manuel Reis
Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637010/local-application-of-bacteria-improves-safety-of-salmonella-mediated-tumor-therapy-and-retains-advantages-of-systemic-infection
#8
Dino Kocijancic, Sebastian Felgner, Tim Schauer, Michael Frahm, Ulrike Heise, Kurt Zimmermann, Marc Erhardt, Siegfried Weiss
Cancer is a devastating disease and a large socio-economic burden. Novel therapeutic solutions are on the rise, although a cure remains elusive. Application of microorganisms represents an ancient therapeutic strategy, lately revoked and refined via simultaneous attenuation and amelioration of pathogenic properties. Salmonella Typhimurium has prevailed in preclinical development. Yet, using virulent strains for systemic treatment might cause severe side effects. In the present study, we highlight a modified strain based on Salmonella Typhimurium UK-1 expressing hexa-acylated Lipid A...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637000/precision-medicine-for-hepatocellular-carcinoma-driver-mutations-and-targeted-therapy
#9
REVIEW
Xiao-Xiao Ding, Qing-Ge Zhu, Shi-Ming Zhang, Lei Guan, Ting Li, Lei Zhang, Shi-Yang Wang, Wan-Li Ren, Xue-Mei Chen, Jing Zhao, Song Lin, Zhi-Zhen Liu, Yan-Xia Bai, Bing He, Hu-Qin Zhang
Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related mortality and there are an estimated approximately 850,000 new cases annually. Most HCC patients are diagnosed at middle or advanced stage, losing the opportunity of surgery. The development of HCC is promoted by accumulated diverse genetic mutations, which confer selective growth advantages to tumor cells and are called "driver mutations". The discovery of driver mutations provides a novel precision medicine strategy for late stage HCC, called targeted therapy...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636992/acetylsalicylic-acid-inhibits-the-growth-of-melanoma-tumors-via-sox2-dependent-paf-r-independent-signaling-pathway
#10
Anita Thyagarajan, Jeremiah Saylae, Ravi P Sahu
Acquired resistance to standard therapies remains a serious challenge, requiring novel therapeutic approaches that incorporate potential factors involved in tumor resistance. As cancers including melanoma express inflammatory cyclooxygenases generating prostaglandins implicated in tumor growth, we investigated mechanism of anti-inflammatory drug, acetylsalicylic acid (ASA) which has been shown to inhibit various tumor types, however, its effects against highly aggressive melanoma model are unclear. Given our reports that an activation of platelet-activating factor-receptor (PAF-R) augments the growth and impede efficacies of therapeutic agents in experimental melanoma, we also sought to determine if PAF-R mediates anti-melanoma activity of ASA...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636985/changes-in-programmed-death-ligand-1-expression-during-cisplatin-treatment-in-patients-with-head-and-neck-squamous-cell-carcinoma
#11
Chan-Young Ock, Sehui Kim, Bhumsuk Keam, Soyeon Kim, Yong-Oon Ahn, Eun-Jae Chung, Jin-Ho Kim, Tae Min Kim, Seong Keun Kwon, Yoon Kyung Jeon, Kyeong Chun Jung, Dong-Wan Kim, Hong-Gyun Wu, Myung-Whun Sung, Dae Seog Heo
Programmed death-ligand 1 (PD-L1) expression is regarded as a predictive marker for anti-PD-1/PD-L1 therapy. The purpose of study was to explore the changes in PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) during treatment. Paired HNSCC tissues prior to and after cisplatin-based treatment were evaluated to determine PD-L1 protein expression by immunohistochemistry. Among the 35 HNSCC patient samples, PD-L1 expression status changed after treatment in 37.1% (13/35) of samples. Among the 13 patients whose baseline PD-L1 was negative, PD-L1 expression was increased in 9 cases (69...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636979/exosomes-in-diagnosis-and-therapy-of-prostate-cancer
#12
REVIEW
Jun Pan, Meng Ding, Kai Xu, Chunhua Yang, Li-Jun Mao
Exosomes are small vesicular bodies released by a variety of cells. Exosomes contain miRNAs, mRNAs and proteins with the potential to regulate signaling pathways in recipient cells. Exosomes deliver nucleic acids and proteins to mediate the communication between cancer cells and stroma cells. In this review, we summarize recent progress in our understanding of the role of exosomes in prostate cancer. The tumorigenesis, metastasis and drug resistance of prostate cancer are associated with the cargos of exosomes such as miRNAs, lncRNAs and proteins...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636962/reactive-astrocytes-production-function-and-therapeutic-potential
#13
REVIEW
Shane A Liddelow, Ben A Barres
Astrocytes constitute approximately 30% of the cells in the mammalian central nervous system (CNS). They are integral to brain and spinal-cord physiology and perform many functions important for normal neuronal development, synapse formation, and proper propagation of action potentials. We still know very little, however, about how these functions change in response to immune attack, chronic neurodegenerative disease, or acute trauma. In this review, we summarize recent studies that demonstrate that different initiating CNS injuries can elicit at least two types of "reactive" astrocytes with strikingly different properties, one type being helpful and the other harmful...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636955/inflammatory-ly6c-high-monocytes-protect-against-candidiasis-through-il-15-driven-nk-cell-neutrophil-activation
#14
Jorge Domínguez-Andrés, Lidia Feo-Lucas, María Minguito de la Escalera, Leticia González, María López-Bravo, Carlos Ardavín
Neutrophils play a crucial role in defense against systemic candidiasis, a disease associated with a high mortality rate in patients receiving immunosuppressive therapy, although the early immune mechanisms that boost the candidacidal activity of neutrophils remain to be defined in depth. Here, we used a murine model of systemic candidiasis to explore the role of inflammatory Ly6C(high) monocytes in NK cell-mediated neutrophil activation during the innate immune response against C. albicans. We found that efficient anti-Candida immunity required a collaborative response between the spleen and kidney, which relied on type I interferon-dependent IL-15 production by spleen inflammatory Ly6C(high) monocytes to drive efficient activation and GM-CSF release by spleen NK cells; this in turn was necessary to boost the Candida killing potential of kidney neutrophils...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636942/extensive-proliferation-of-human-cancer-cells-with-ever-shorter-telomeres
#15
Rebecca A Dagg, Hilda A Pickett, Axel A Neumann, Christine E Napier, Jeremy D Henson, Erdahl T Teber, Jonathan W Arthur, C Patrick Reynolds, Jayne Murray, Michelle Haber, Alexander P Sobinoff, Loretta M S Lau, Roger R Reddel
Acquisition of replicative immortality is currently regarded as essential for malignant transformation. This is achieved by activating a telomere lengthening mechanism (TLM), either telomerase or alternative lengthening of telomeres, to counter normal telomere attrition. However, a substantial proportion of some cancer types, including glioblastomas, liposarcomas, retinoblastomas, and osteosarcomas, are reportedly TLM-negative. As serial samples of human tumors cannot usually be obtained to monitor telomere length changes, it has previously been impossible to determine whether tumors are truly TLM-deficient, there is a previously unrecognized TLM, or the assay results are false-negative...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636941/highly-aggressive-metastatic-melanoma-cells-unable-to-maintain-telomere-length
#16
Nikenza Viceconte, Marie-Sophie Dheur, Eva Majerova, Christophe E Pierreux, Jean-François Baurain, Nicolas van Baren, Anabelle Decottignies
Unlimited replicative potential is one of the hallmarks of cancer cells. In melanoma, hTERT (telomerase reverse transcriptase) is frequently overexpressed because of activating mutations in its promoter, suggesting that telomerase is necessary for melanoma development. We observed, however, that a subset of melanoma metastases and derived cell lines had no telomere maintenance mechanism. Early passages of the latter displayed long telomeres that progressively shortened and fused before cell death. We propose that, during melanoma formation, oncogenic mutations occur in precursor melanocytes with long telomeres, providing cells with sufficient replicative potential, thereby bypassing the need to re-activate telomerase...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636928/neurovascular-toxicity-of-n-methyl-d-aspartate-is-markedly-enhanced-in-the-developing-mouse-central-nervous-system
#17
Sudhakar Vadivelu, Kui Xu, Vanja Tolj, Rahul Rege, Lindsay Darkins, Karthik Vishwanath
Penumbral perfusion is critical to brain viability. Proximal arterial occlusion and deep brain stroke has variable effect on cortical dysfunction. Cortical microvessel collaterals may be recruited and at times sufficient for partial parenchymal perfusion. Postnatal neural and endothelial cells are markedly vulnerable to glutamate excitotoxicity. Early vascular cell stress may promote partial protective neural preconditioning though postnatally a developmental window of the cerebral microvasculature may be particularly vulnerable to injury...
June 18, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28636901/the-effect-of-cd34-cell-telomere-length-and-htert-expression-on-the-outcome-of-autologous-cd34-cell-transplantation-in-patients-with-chronic-heart-failure
#18
Jasmina-Ziva Rozman, Maja Pohar Perme, Mojca Jez, Elvira Malicev, Metka Krasna, Srdjan Novakovic, Bojan Vrtovec, Primoz Rozman
Age-related telomere attrition in stem/progenitor cells may diminish their functional capacity and thereby impair the outcome of cell-based therapies. The aim of the present study was to investigate the effect of CD34(+) cell telomere length and hTERT expression on the clinical outcome of autologous CD34(+) cell transplantation. We studied 43 patients with cardiomyopathy. Their peripheral blood CD34(+) cells were mobilized with granulocyte colony-stimulating factor, enriched by immunoselection and delivered transendocardially...
June 18, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28636891/comparison-of-cyclophosphamide-thalidomide-dexamethasone-to-bortezomib-cyclophosphamide-dexamethasone-as-induction-therapy-for-multiple-myeloma-patients-in-brazil
#19
Suelen Vigolo, Joice Zuckermann, Rosane Isabel Bittencourt, Lúcia Silla, Diogo André Pilger
OBJECTIVE/BACKGROUND: Chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) remains the standard treatment for multiple myeloma (MM). Thalidomide or bortezomib may be combined with cyclophosphamide and dexamethasone, in what are known as the CTD and VCD protocols, respectively. The objective of this study was to evaluate the clinical characteristics and response rates obtained with CTD and VCD, observing whether the inclusion of bortezomib to treat MM patients in Brazil increases therapeutic efficiency...
June 15, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28636889/complications-of-hematopoietic-stem-transplantation-fungal-infections
#20
REVIEW
Ali S Omrani, Reem S Almaghrabi
Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of invasive fungal infections, especially during the early neutropenic phase and severe graft-versus-host disease. Mold-active prophylaxis should be limited to the highest risk groups. Empiric antifungal therapy for HSCT with persistent febrile neutropenia is associated with unacceptable response rates, unnecessary antifungal therapy, increased risk of toxicity, and inflated costs. Empiric therapy should not be a substitute for detailed work up to identify the cause of fever in such patients...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
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