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https://www.readbyqxmd.com/read/28332219/targeting-immunotherapy-to-the-tumor-microenvironment
#1
Michael Dougan, Stephanie K Dougan
Targeting drugs to the tumor microenvironment has long been appreciated as a means of increasing local concentrations and decreasing systemic toxicities. How drug targeting might apply to immune-based therapies is less clear. In this review, we explain the immunology of cancer, with a focus on the principles of in situ vaccination. Certain types of therapies are more amenable to local versus systemic delivery; these include cytokines, adjuvants, radiation, and agents targeting tumor-resident cell populations...
March 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28331999/the-acidic-microenvironment-as-a-possible-niche-of-dormant-tumor-cells
#2
REVIEW
Silvia Peppicelli, Elena Andreucci, Jessica Ruzzolini, Anna Laurenzana, Francesca Margheri, Gabriella Fibbi, Mario Del Rosso, Francesca Bianchini, Lido Calorini
Although surgical excision, chemo-, and radio-therapy are clearly advanced, tumors may relapse due to cells of the so-called "minimal residual disease". Indeed, small clusters of tumor cells persist in host tissues after treatment of the primary tumor elaborating strategies to survive and escape from immunological attacks before their relapse: this variable period of remission is known as "cancer dormancy". Therefore, it is crucial to understand and consider the major concepts addressing dormancy, to identify new targets and disclose potential clinical strategies...
March 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28329346/posttreatment-reactions-after-single-dose-diethylcarbamazine-or-ivermectin-in-subjects-with-loa-loa-infection
#3
Jesica A Herrick, Fanny Legrand, Raceline Gounoue, Godwin Nchinda, Céline Montavon, Jean Bopda, Steve Mbickmen Tchana, Bienvenu Etogo Ondigui, Konrad Nguluwe, Michael P Fay, Michelle Makiya, Simon Metenou, Thomas B Nutman, Joseph Kamgno, Amy D Klion
Background.: Severe adverse reactions have been observed in individuals with Loa loa infection treated with either diethylcarbamazine (DEC), the drug of choice for loiasis, or ivermectin (IVM), which is used in mass drug administration programs for control of onchocerciasis and lymphatic filariasis in Africa. In this study, posttreatment clinical and immunologic reactions were compared following single-dose therapy with DEC or IVM to assess whether these reactions have the same underlying pathophysiology...
March 13, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28329080/differences-in-immunologic-factors-among-patients-presenting-with-altered-mental-status-during-cryptococcal-meningitis
#4
Sarah Lofgren, Kathy H Hullsiek, Bozena M Morawski, Henry W Nabeta, Reuben Kiggundu, Kabanda Taseera, Abdu Musubire, Charlotte Schutz, Mahsa Abassi, Nathan C Bahr, Lillian Tugume, Conrad Muzoora, Darlisha A Williams, Melissa A Rolfes, Sruti S Velamakanni, Radha Rajasingham, Graeme Meintjes, Joshua Rhein, David B Meya, David R Boulware
Altered mental status in cryptococcal meningitis results in poorer survival, but underlying causes of altered mentation are poorly understood. Within two clinical trials, we assessed risk factors for altered mental status (GCS score<15) considering baseline clinical characteristics, CSF cytokines/chemokines, and antiretroviral therapy. Among 326 enrolled participants, 97 (30%) had GCS<15 and these patients had lower median CSF cryptococcal antigen titers (P=0.042) and CCL2 (P=0.005) but higher opening pressures (320 vs...
January 30, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28326065/antifungal-therapy-for-systemic-mycosis-and-the-nanobiotechnology-era-improving-efficacy-biodistribution-and-toxicity
#5
REVIEW
Ana C O Souza, Andre C Amaral
Fungal diseases have been emerging as an important public health problem worldwide with the increase in host predisposition factors due to immunological dysregulations, immunosuppressive and/or anticancer therapy. Antifungal therapy for systemic mycosis is limited, most of times expensive and causes important toxic effects. Nanotechnology has become an interesting strategy to improve efficacy of traditional antifungal drugs, which allows lower toxicity, better biodistribution, and drug targeting, with promising results in vitro and in vivo...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28325288/retroviral-replicating-vector-delivery-of-mir-pdl1-inhibits-immune-checkpoint-pdl1-and-enhances-immune-responses-in%C3%A2-vitro
#6
Amy H Lin, Christopher G Twitty, Ryan Burnett, Andrew Hofacre, Leah A Mitchell, Fernando Lopez Espinoza, Harry E Gruber, Douglas J Jolly
Tumor cells express a number of immunosuppressive molecules that can suppress anti-tumor immune responses. Efficient delivery of small interfering RNAs to treat a wide range of diseases including cancers remains a challenge. Retroviral replicating vectors (RRV) can be used to stably and selectively introduce genetic material into cancer cells. Here, we designed RRV to express shRNA (RRV-shPDL1) or microRNA30-derived shRNA (RRV-miRPDL1) using Pol II or Pol III promoters to downregulate PDL1 in human cancer cells...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325250/radiotherapy-in-the-age-of-cancer-immunology-current-concepts-and-future-developments
#7
REVIEW
Mauro Loi, Isacco Desideri, Daniela Greto, Monica Mangoni, Mariangela Sottili, Icro Meattini, Carlotta Becherini, Francesca Terziani, Camilla Delli Paoli, Emanuela Olmetto, Pierluigi Bonomo, Lorenzo Livi
Major advances in the knowledge of cancer biology and its interactions with tumor immune environment led to the emergence, in the last five years of new immunotherapy-based treatment strategies in cancer patients. At the same time, improvement in radiation technique and progress in radiobiology allowed in the last decade to expand the applications of radiotherapy in a growing number of settings. At present, there are strong theoretical basis to propose immune-enhanced radiation therapy that may represent in the future a new paradigm of treatment, combining the intrinsic power of radiotherapy to elicit a specific, systemic, tumor-directed immune response with modern highly conformal and precise dose delivery, in order to maximize response at the major site of disease and obtain durable disease control...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28323111/nanoparticles-for-tumor-immunotherapy
#8
REVIEW
Xinlong Zang, Xiuli Zhao, Haiyang Hu, Mingxi Qiao, Yihui Deng, Dawei Chen
Although most researches and therapies have been focused on the tumor itself, it is becoming clear that immune cells can not only suppress tumor development but support and maintain their malignant type. Promising recent developments in immunology will provide opportunities for tumor-specific immunotherapy, which can orchestrate the patients immune system to target, fight and eradicate cancer cells without destroying healthy cells. However, antitumor immunity driven by self-immune system alone may be therapeutically insufficient...
March 18, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28321217/a-vaccine-therapy-for-canine-visceral-leishmaniasis-promoted-significant-improvement-of-clinical-and-immune-status-with-reduction-in-parasite-burden
#9
Bruno Mendes Roatt, Rodrigo Dian de Oliveira Aguiar-Soares, Levi Eduardo Soares Reis, Jamille Mirelle de Oliveira Cardoso, Fernando Augusto Siqueira Mathias, Rory Cristiane Fortes de Brito, Sydnei Magno da Silva, Nelder De Figueiredo Gontijo, Sidney de Almeida Ferreira, Jesus G Valenzuela, Rodrigo Corrêa-Oliveira, Rodolfo Cordeiro Giunchetti, Alexandre Barbosa Reis
Herein, we evaluated the treatment strategy employing a therapeutic heterologous vaccine composed of antigens of Leishmania braziliensis associated with MPL adjuvant (LBMPL vaccine) for visceral leishmaniasis (VL) in symptomatic dogs naturally infected by Leishmania infantum. Sixteen dogs received immunotherapy with MPL adjuvant (n = 6) or with a vaccine composed of antigens of L. braziliensis associated with MPL (LBMPL vaccine therapy, n = 10). Dogs were submitted to an immunotherapeutic scheme consisting of 3 series composed of 10 subcutaneous doses with 10-day interval between each series...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28320438/regulatory-t-cell-frequency-but-not-plasma-il-33-levels-represents-potential-immunological-biomarker-to-predict-clinical-response-to-intravenous-immunoglobulin-therapy
#10
Mohan S Maddur, Emmanuel Stephen-Victor, Mrinmoy Das, Praveen Prakhar, Varun K Sharma, Vikas Singh, Magalie Rabin, Jamma Trinath, Kithiganahalli N Balaji, Francis Bolgert, Jean-Michel Vallat, Laurent Magy, Srini V Kaveri, Jagadeesh Bayry
BACKGROUND: Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (Treg) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. METHODS: Ten newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0...
March 20, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28320105/anti-fibrotic-potential-of-human-umbilical-cord-mononuclear-cells-and-mouse-bone-marrow-cells-in-ccl4-induced-liver-fibrosis-in-mice
#11
Nageh Ahmed Elmahdy, Samia Salem Sokar, Mohamed Labib Salem, Naglaa Ibrahim Sarhan, Sherin Hamed Abou-Elela
Liver fibrosis is the consequence of hepatocyte injury that leads to the activation of hepatic stellate cells (HSC). The treatment of choice is Liver transplantation; however, it has many problems such as surgery-related complications, immunological rejection and high costs associated with the procedure. Stem cell-based therapy would be a potential alternative, so the aim of this study is to investigate the therapeutic potential of human umbilical cord mononuclear cells (MNC) and mouse bone marrow cells (BMC) against carbon tetrachloride (CCl4) induced liver fibrosis in mice and compare it with that of silymarin...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319779/supramolecular-biofunctional-materials
#12
REVIEW
Jie Zhou, Jie Li, Xuewen Du, Bing Xu
This review discusses supramolecular biofunctional materials, a novel class of biomaterials formed by small molecules that are held together via noncovalent interactions. The complexity of biology and relevant biomedical problems not only inspire, but also demand effective molecular design for functional materials. Supramolecular biofunctional materials offer (almost) unlimited possibilities and opportunities to address challenging biomedical problems. Rational molecular design of supramolecular biofunctional materials exploit powerful and versatile noncovalent interactions, which offer many advantages, such as responsiveness, reversibility, tunability, biomimicry, modularity, predictability, and, most importantly, adaptiveness...
March 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28319446/good-laboratory-practice-preclinical-safety-studies-for-gsk2696273-mlv-vector-based-ex-vivo-gene-therapy-for-adenosine-deaminase-deficiency-severe-combined-immunodeficiency-in-nsg-mice
#13
Nicola Carriglio, Jan Klapwijk, Raisa Jofra Hernandez, Michela Vezzoli, Franck Chanut, Rhiannon Lowe, Draghici Elena, Melanie Nord, Paola Albertini, Patrizia Cristofori, Jane Richards, Hazel Staton, Jonathan Appleby, Alessandro Aiuti, Aisha V Sauer
GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28318808/t-cell-receptor-assessment-in-autoimmune-disease-requires-access-to-the-most-adjacent-immunologically-active-organ
#14
Bergithe E Oftedal, Brita Ardesjö Lundgren, David Hamm, Poh-Yi Gan, Stephen R Holdsworth, Christopher N Hahn, Andreas W Schreiber, Hamish S Scott
Next generation sequencing of T and B cell receptors is emerging as a valuable and effective method to diagnose and monitor hematopoietic malignancies. So far, this approach has not been fully explored in regard to autoimmune diseases. T cells develop in the thymus where they undergo positive and negative selection, and the autoimmune regulator (Aire) is central in the establishment of immunological tolerance. Loss of Aire leads to severe multiorgan autoimmune disease with infiltration of autoreactive T cells in affected organs...
March 15, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28318556/natural-killer-cells-in-placentation-and-cancer-implications-for-hypertension-during-pregnancy
#15
Heather Yvonne Small, Denise C Cornelius, Tomasz J Guzik, Christian Delles
Hypertension during pregnancy is the most common medical condition encountered during gestation. Despite this, knowledge of the mechanisms that underlie the disease and the development of new therapies are limited. Hypertension during pregnancy and some forms of cancer confer an increased risk to the development of cardiovascular disease later in life; one mechanism which may link these conditions is the involvement of natural killer (NK) cells. Whilst immunology and immunotherapy are well-developed areas in oncology; the complex mechanisms of the immune system in health and disease at the maternal-fetal interface are less well-defined...
March 7, 2017: Placenta
https://www.readbyqxmd.com/read/28317620/lupus-hepatitis-and-autoimmune-hepatitis-lupoid-hepatitis
#16
REVIEW
Avinash Adiga, Kenneth Nugent
Liver dysfunction occurs in approximately 50% of patients with systemic lupus erythematosus (SLE), and patients with SLE and elevated liver enzymes can present a complicated and difficult differential diagnosis. Lupus hepatitis and autoimmune hepatitis are 2 immunologic conditions involving the liver, which can have similar clinical, laboratory and systemic presentations, leading to difficulties in diagnosis. Physicians need to be aware of these 2 hepatic diseases as diagnosis and appropriate therapy need to occur early in the disease course to prevent progression to advanced liver disease...
April 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28317087/imaging-and-clinicopathological-features-of-nivolumab-related-cholangitis-in-patients-with-non-small-cell-lung-cancer
#17
Hisato Kawakami, Junko Tanizaki, Kaoru Tanaka, Koji Haratani, Hidetoshi Hayashi, Masayuki Takeda, Ken Kamata, Mamoru Takenaka, Masatomo Kimura, Takaaki Chikugo, Takao Sato, Masatoshi Kudo, Akihiko Ito, Kazuhiko Nakagawa
Background Nivolumab demonstrates promising efficacy for the treatment of non-small cell lung cancer and other malignancies. The clinical benefit of nivolumab, however, may be hampered by specific immune-related adverse events (irAEs), and little is known regarding nivolumab-related cholangitis. Methods A computerized search of our clinical database identified 3 metastatic non-small cell lung cancer patients with nivolumab-related cholangitis. All patients were treated with intravenous nivolumab monotherapy (3...
March 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28316970/dgk-%C3%AE-a-checkpoint-in-cancer-mediated-immuno-inhibition-and-target-for-immunotherapy
#18
Elfriede Noessner
Immunotherapy is moving to the forefront of cancer treatments owing to impressive durable responses achieved with checkpoint blockade antibodies and adoptive T-cell therapy. Still, improvements are necessary since, overall, only a small percentage of patients benefit from current therapies. Here, I summarize evidence that DGK-α may represent an immunological checkpoint suppressing the activity of cytotoxic immunocytes in the tumor microenvironment. DGK-inhibitors can restore the antitumor function of tumor-suppressed adaptive and innate cytotoxic immunocytes...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28315228/clinical-value-of-monoclonal-antibodies-and-tyrosine-kinase-inhibitors-in-the-treatment-of-head-and-neck-squamous-cell-carcinoma
#19
REVIEW
Wiktoria Blaszczak, Wojciech Barczak, Anna Wegner, Wojciech Golusinski, Wiktoria Maria Suchorska
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of malignant tumours that affects over 500,000 patients per year. Treatment failure is generally due to the heterogeneity of these tumours and to the serious adverse effects associated with treatment. Immunological system impairment, which is common in HNSCC, further contributes to treatment failure by mediating tumour escape mechanisms. To date, the only clinically approved targeted therapy agent is cetuximab, a monoclonal antibody (mAb) that binds to, and inhibits, epidermal growth factor receptor, which is widely overexpressed in HNSCC...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28314313/pd-l1-expression-confers-better-prognosis-in-locally-advanced-oral-squamous-cell-carcinoma
#20
Yasunao Kogashiwa, Masanori Yasuda, Hiroyuki Sakurai, Mitsuhiko Nakahira, Yoshie Sano, Kenji Gonda, Tetsuya Ikeda, Hitoshi Inoue, Kiyomi Kuba, Susumu Oba, Junichi Ishikawa, Yuichiro Enoki, Satoko Matsumura, Kazuhiko Minami, Yasuhiro Ebihara, Masashi Sugasawa
BACKGROUND/AIM: Clinical trials with therapies targeting immune checkpoint molecules have shown promising results in several tumor types. However, the predictive and prognostic values of these immunological factors for locally advanced oral squamous cell carcinomas (LAOSCC) remain unclear. Our purpose was to evaluate the expression and prognostic value of programmed cell death-ligand1 (PD-L1) and PD-L2 and to correlate their expression with the degree of infiltration by CD8(+) cells in LAOSCC...
March 2017: Anticancer Research
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