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Manglio Rizzo, Laura Alaniz, Guillermo D Mazzolini
In recent years immunotherapy has revolutionized the treatment of patients with advanced cancer. The increased knowledge in the tumor immune-biology has allowed developing rational treatments by manipulation of the immune system with significant clinical impact. This rapid development has significantly changed the prognosis of many tumors without treatment options up to date. Other strategies have explored the use of therapeutic vaccines based on dendritic cells (DC) by inducing antitumor immunity. DC are cells of hematopoietic origin, constitutively expressing molecules capable to present antigens, that are functionally the most potent inducers of the activation and proliferation of antigen specific T lymphocytes...
2016: Medicina
Stephan Grabbe, Heinrich Haas, Mustafa Diken, Lena M Kranz, Peter Langguth, Ugur Sahin
The development of nucleic acid based vaccines against cancer has gained considerable momentum through the advancement of modern sequencing technologies and on novel RNA-based synthetic drug formats, which can be readily adapted following identification of every patient's tumor-specific mutations. Furthermore, affordable and individual 'on demand' production of molecularly optimized vaccines should allow their application in large groups of patients. This has resulted in the therapeutic concept of an active personalized cancer vaccine, which has been brought into clinical testing...
October 2016: Nanomedicine
Alberto C Guardo, Patrick Tjok Joe, L Miralles, M E Bargalló, B Mothe, A Krasniqi, C Heirman, F García, Kris Thielemans, Christian Brander, Joeri L Aerts, Montserrat Plana
BACKGROUND: The development of a prophylactic vaccine against HIV-1 has so far not been successful. Therefore, attention has shifted more and more towards the development of novel therapeutic vaccines. Here, we evaluated a new mRNA based therapeutic vaccine against HIV-1 encoding activation signals (TriMix: CD40L+CD70+caTLRA4) combined with rationally selected antigenic sequences (HTI sequence: comprised of 16 joined fragments from Gag, Pol, Vif and Nef). METHODS: For this purpose, PBMC from HIV-1-infected individuals on cART, lymph node explants from non-infected humans and splenocytes from immunized mice were collected and several immune functions were measured...
September 24, 2016: AIDS
Elizabeth Scheid, Pierre Major, Alain Bergeron, Olivera J Finn, Russell D Salter, Robin Eady, Bader Yassine-Diab, David Favre, Yoav Peretz, Claire Landry, Sebastien Hotte, Som D Mukherjee, Gregory A Dekaban, Corby Fink, Paula J Foster, Jeffery Gaudet, Jean Gariepy, Rafick-Pierre Sekaly, Louis Lacombe, Yves Fradet, Ronan Foley
MUC1 is a glycoprotein expressed on the apical surface of ductal epithelial cells. Malignant transformation results in loss of polarization and overexpression of hypoglycosylated MUC1 carrying truncated carbohydrates known as T or Tn tumor antigens. Tumor MUC1 bearing Tn carbohydrates (Tn-MUC1) represent a potential target for immunotherapy. We evaluated the Tn-MUC1 glycopeptide in a human phase I/II clinical trial for safety that followed a preclinical study of different glycosylation forms of MUC1 in rhesus macaques, whose MUC1 is highly homologous to human MUC1...
October 2016: Cancer Immunology Research
Maxim G Itkin, Francis X McCormack, Yoav Dori
RATIONALE: Plastic bronchitis is a condition characterized by expectoration of branching bronchial casts. Although the mechanism of cast formation in adults with plastic bronchitis remains poorly understood, abnormal pulmonary lymphatic flow resulting in molding of congealing lymphatic fluids in the airway has been documented as a cause of the disease in children with congenital heart disease. OBJECTIVES: To use advanced lymphatic imaging techniques, including dynamic contrast-enhanced magnetic resonance (MR) lymphangiography (DCMRL) and intranodal lymphangiography, to investigate the mechanism of cast formation in adult patients with plastic bronchitis, and to evaluate the therapeutic outcome of percutaneous lymphatic embolization for these patients...
October 2016: Annals of the American Thoracic Society
Tetsuya Kodama, Daisuke Matsuki, Asuka Tada, Kazu Takeda, Shiro Mori
Intravenous chemotherapy has poor access to metastatic lymph nodes (LNs) and is limited by short-lived drug concentrations. Here, we describe the administration of chemotherapy via the lymphatic network as a new concept for the prevention and treatment of metastatic LNs. A metastatic LN can be treated by the injection of drugs into an upstream LN, either the sentinel LN (SLN) or another upstream LN. In a mouse model, tumor cells were inoculated into the subiliac LN (SiLN) to induce metastasis to the proper axillary LN (PALN)...
September 1, 2016: Scientific Reports
Ans De Beuckelaer, Charlotte Pollard, Sandra Van Lint, Kenny Roose, Lien Van Hoecke, Thomas Naessens, Vimal Kumar Udhayakumar, Muriel Smet, Niek Sanders, Stefan Lienenklaus, Xavier Saelens, Siegfried Weiss, Guido Vanham, Johan Grooten, Stefaan De Koker
Given their high potential to evoke cytolytic T cell responses, tumour antigen-encoding mRNA vaccines are now being intensively explored as therapeutic cancer vaccines. mRNA vaccines clearly benefit from wrapping the mRNA into nano-sized carriers such as lipoplexes that protect the mRNA from degradation and increase its uptake by dendritic cells in vivo. Nevertheless, the early innate host factors that regulate the induction of cytolytic T cells to mRNA lipoplex vaccines have remained unresolved. Here, we demonstrate that mRNA lipoplexes induce a potent type I IFN response upon subcutaneous, intradermal and intranodal injection...
August 10, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Namik Kemal Altinbas, Ilker Oz, Evren Ustuner, Basak Gulpinar, Elif Peker, Zehra Akkaya, Ahmet Peker, Koray Ceyhan, Cemil Yagci
BACKGROUND: Intranodal palisaded myofibroblastoma is a benign and very rare mesenchymal neoplasm of the lymph nodes originating from differentiated smooth muscle cells and myofibroblasts. CASE REPORT: We report a case of intranodal palisaded myofibroblastoma in an 84-year-old woman with Parkinson's disease that presented as a left inguinal mass. The diagnosis was made using ultrasound-guided fine needle aspiration biopsy and consequent cytopathological examination that included immunohistochemical analysis...
2016: Polish Journal of Radiology
Yasemin Yuyucu Karabulut, Tuba Kara, Mustafa Berkeşoğlu
Intranodal palisaded myofibroblastoma (IPM) is a benign mesenchymal neoplasm originating from smooth muscle cells and myofibroblasts. The inguinal region is the most common site of this rare tumor. As there are only about 89 such cases reported in the literature, the precise etiology and pathogenesis have yet to be explained adequately. It is characterized by spindle cells, amianthoid fibers, and by the proliferation of hemosiderin-containing histiocytes in the lymph node. A nodular lesion was excised from the inguinal region of a 47-year-old female patient with the clinical diagnosis of lymphoma and/or metastase...
October 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Christopher R Gilbert, Catherine Abendroth, Lonny B Yarmus
The presence of intrathoracic lymphadenopathy in patients with suspected malignancy remains concerning, often prompting further evaluation with tissue sampling. The presence of nodal granulomatous inflammation in patients with underlying malignancy is well reported. However, review of 3 recent large trials of endobronchial ultrasound-guided transbronchial needle aspiration in patients with granulomatous inflammation and malignancy did not identify the presence of coexisting, intranodal malignancy, and granulomatous inflammation, rather these diagnoses remained nodally exclusive...
July 29, 2016: Journal of Bronchology & Interventional Pulmonology
Mario Novkovic, Lucas Onder, Jovana Cupovic, Jun Abe, David Bomze, Viviana Cremasco, Elke Scandella, Jens V Stein, Gennady Bocharov, Shannon J Turley, Burkhard Ludewig
Fibroblastic reticular cells (FRCs) form the cellular scaffold of lymph nodes (LNs) and establish distinct microenvironmental niches to provide key molecules that drive innate and adaptive immune responses and control immune regulatory processes. Here, we have used a graph theory-based systems biology approach to determine topological properties and robustness of the LN FRC network in mice. We found that the FRC network exhibits an imprinted small-world topology that is fully regenerated within 4 wk after complete FRC ablation...
July 2016: PLoS Biology
Claudio Luchini, Laura D Wood, Liang Cheng, Alessia Nottegar, Brendon Stubbs, Marco Solmi, Paola Capelli, Antonio Pea, Giuseppe Sergi, Enzo Manzato, Matteo Fassan, Fabio Bagante, Elfriede Bollschweiler, Simone Giacopuzzi, Takuma Kaneko, Giovanni de Manzoni, Mattia Barbareschi, Aldo Scarpa, Nicola Veronese
The extranodal extension (ENE) of nodal metastasis is the extension of neoplastic cells through the nodal capsule into the perinodal adipose tissue. This histological feature has recently been indicated as an important prognostic factor in different types of malignancies; in this manuscript, we aim at defining its role in the prognosis of oesophageal cancer with the tool of meta-analysis. Two independent authors searched SCOPUS and PubMed until 31 August 2015 without language restrictions. The studies with available data about prognostic parameters in subjects with oesophageal cancer, comparing patients with the presence of ENE (ENE+) versus only intranodal extension (ENE-), were considered as eligible...
July 7, 2016: Journal of Clinical Pathology
Ivan H W Yim, Malcolm B Will, Catharine Dhaliwal, Donald M Salter, William S Walker
Intranodal palisaded myofibroblastoma is a rare and benign tumor that usually presents in the inguinal region. We report the case of a 68-year-old woman with a right paratracheal mass and right upper lobe non-small cell lung carcinoma initially staged as T1b N2 M0. After mediastinal staging, the right paratracheal mass was found to be an intranodal palisaded myofibroblastoma, which had caused erroneous upstaging of the lung carcinoma to N2 disease. This had the potential of leading to suboptimal treatment of the primary lung carcinoma if formal mediastinal staging had not been performed...
July 2016: Annals of Thoracic Surgery
Anne M Stowman, Stacey E Mills, Mark R Wick
Intranodal spindle cell lesions on biopsy are problematic for a surgical pathologist, often requiring an extensive immunohistochemical evaluation with variable and frequently unsatisfactory results. In the absence of a history of malignancy, the differential diagnosis of a spindle cell tumor must include both a primary nodal proliferation and a metastatic process. Particularly challenging are those lesions that share morphologic and immunohistochemical features; spindle cell melanomas (SCM) and interdigitating dendritic cell sarcomas (IDCS) belong to this category...
September 2016: American Journal of Surgical Pathology
Deepankar Misra, Sapna Panjwani, Shalu Rai, Akansha Misra, Mukul Prabhat, Prashant Gupta, Subrata K Talukder
BACKGROUND: To evaluate the efficacy of color Doppler ultrasound (CDUS) in differentiating benign and malignant cervical lymph nodes by detecting differences in blood flow patterns. MATERIALS AND METHODS: In this cross-sectional prospective study, 25 untreated patients with clinical evidence of cervical lymphadenopathy were evaluated. CDUS was performed for 80 cervical lymph nodes. The gray scale parameters of the lymph node and intranodal perfusion sites were the key CDUS features used to differentiate between reactive and metastatic lymph nodes...
May 2016: Dental Research Journal
Valentina Salvi, William Vermi, Veronica Gianello, Silvia Lonardi, Vincenzo Gagliostro, Antonella Naldini, Silvano Sozzani, Daniela Bosisio
Lymph node expansion during inflammation is essential to establish immune responses and relies on the development of blood and lymph vessels. Previous work in mice has shown that this process depends on the presence of VEGF-A produced by B cells, macrophages and stromal cells. In humans, however, the cell types and the mechanisms regulating the intranodal production of VEGF-A remain elusive. Here we show that CD11c+ cells represent the main VEGF-A-producing cell population in human reactive secondary lymphoid organs...
May 31, 2016: Oncotarget
Sebastian Kreiter, Mustafa Diken, Abderraouf Selmi, Jutta Petschenka, Özlem Türeci, Ugur Sahin
Intranodal immunization with antigen-encoding naked mRNA has proven to be an efficacious and safe approach to induce antitumor immunity. Thanks to its unique characteristics, mRNA can act not only as a source for antigen but also as an adjuvant for activation of the immune system. The search for additional adjuvants that can be combined with mRNA to further improve the potency of the immunization revealed Fms-like tyrosine kinase 3 (FLT3) ligand as a potent candidate. Systemic administration of the dendritic cell-activating FLT3 ligand prior to or along with mRNA immunization-enhanced priming and expansion of antigen-specific CD8(+) T cells in lymphoid organs, T-cell homing into melanoma tumors, and therapeutic activity of the intranodally administered mRNA...
2016: Methods in Molecular Biology
Piero Procacci
We present a new release (6.0β) of the ORAC program [Marsili et al. J. Comput. Chem. 2010, 31, 1106-1116] with a hybrid OpenMP/MPI (open multiprocessing message passing interface) multilevel parallelism tailored for generalized ensemble (GE) and fast switching double annihilation (FS-DAM) nonequilibrium technology aimed at evaluating the binding free energy in drug-receptor system on high performance computing platforms. The production of the GE or FS-DAM trajectories is handled using a weak scaling parallel approach on the MPI level only, while a strong scaling force decomposition scheme is implemented for intranode computations with shared memory access at the OpenMP level...
June 27, 2016: Journal of Chemical Information and Modeling
Tae Wook Kong, Suk Joon Chang, Jinoo Kim, Jiheum Paek, Su Hyun Kim, Je Hwan Won, Hee Sug Ryu
OBJECTIVE: To evaluate risk factors for massive lymphatic ascites after laparoscopic retroperitoneal lymphadenectomy in gynecologic cancer and the feasibility of treatments using intranodal lymphangiography (INLAG) with glue embolization. METHODS: A retrospective analysis of 234 patients with gynecologic cancer who received laparoscopic retroperitonal lymphadenectomy between April 2006 and November 2015 was done. In June 2014, INLAG with glue embolization was initiated to manage massive lymphatic ascites...
July 2016: Journal of Gynecologic Oncology
Michael Ying, Sammy C H Cheng, Anil T Ahuja
Ultrasound is useful in assessing cervical lymphadenopathy. Advancement of computer science technology allows accurate and reliable assessment of medical images. The aim of the study described here was to evaluate the diagnostic accuracy of computer-aided assessment of the intranodal vascularity index (VI) in differentiating the various common causes of cervical lymphadenopathy. Power Doppler sonograms of 347 patients (155 with metastasis, 23 with lymphoma, 44 with tuberculous lymphadenitis, 125 reactive) with palpable cervical lymph nodes were reviewed...
August 2016: Ultrasound in Medicine & Biology
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