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E C Martino, G Misso, P Pastina, S Costantini, F Vanni, C Gandolfo, C Botta, F Capone, A Lombardi, L Pirtoli, P Tassone, C Ulivieri, P Tagliaferri, M G Cusi, M Caraglia, P Correale
The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects...
2016: Cell Death Discovery
Hector R Martínez, César E Escamilla-Ocañas, Juan Miguel Tenorio-Pedraza, David Gómez-Almaguer, Jose Carlos Jaime-Perez, Leticia A Olguín-Ramírez, Sergio Salazar-Marioni, María Teresa González-Garza
INTRODUCTION: Increased cytokine expression is a prominent finding in amyotrophic lateral sclerosis (ALS). Due to their interdependence and pleiotropism, interpretation of CSF concentrations of a single cytokine is challenging. We describe a cytokine analysis in ALS patients using a pathway-based statistical method to identify changes in the whole cytokine network. METHODS: We analyzed 19 cytokines in CSF of ALS patients and controls. An equality of concentration matrices was conducted that allowed us to evaluate disturbances in the relationship of cytokines between controls and ALS patients with less and more than 12months of disease length...
October 11, 2016: Cytokine
Line S Bisgaard, Christina K Mogensen, Alexander Rosendahl, Helena Cucak, Lars Bo Nielsen, Salka E Rasmussen, Tanja X Pedersen
Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE-/- mice, their M1/M2 phenotype, inflammatory status, and lipid metabolism signatures were compared. oxLDL accumulation was similar in PEMs and BMDMs. On protein expression level, BMDMs showed an M2-like CD206(high)CD11c(low) profile, while cholesterol loading led to enhanced CD11c expression and reduced MCP-1 secretion...
October 13, 2016: Scientific Reports
Tamara V Smelaya, Olesya B Belopolskaya, Svetlana V Smirnova, Artem N Kuzovlev, Viktor V Moroz, Arkadiy M Golubev, Noel A Pabalan, Lyubov E Salnikova
The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls)...
October 11, 2016: Scientific Reports
Giovanni Grandi, Lucrezia Pignatti, Francesca Ferrari, Giulia Dante, Isabella Neri, Fabio Facchinetti
INTRODUCTION: Inflammation might be an important underlying cause of preterm birth. Our aim is to explore whether vaginal administration α-lipoic acid reduces cervical inflammation and shortening after primary tocolysis. Matherials and Methods: Singleton pregnancies between 24-30 weeks remaining undelivered after hospitalization for preterm labor were randomly allocated to placebo (20 women, 15 analyzed) or vaginal ALA 400 mg daily (20 women, 17 analyzed) for 30 days. A cervical swab to quantify pro-inflammatory (IL1, IL2, IL6, IL8, TNFα) and anti-inflammatory (IL4, IL10) cytokines as well as transvaginal ultrasound cervical length measurement (CL) were performed before and after treatment...
October 9, 2016: Journal of Maternal-fetal & Neonatal Medicine
Iona E Maher, Damien P Higgins
Koala (Phascolarctos cinereus) populations are increasingly vulnerable and one of the main threats is chlamydial infection. Koala retrovirus (KoRV) has been proposed as an underlying cause of the koala's susceptibility to infection with Chlamydia and high rates of lymphoid neoplasia; however, the regionally ubiquitous, endogenous nature of this virus suggests that KoRV A infection is not sufficient for immune suppression to occur. A recently discovered exogenous variant of KoRV, KoRV B, has several structural elements that cause increased pathogenicity in related retroviruses and was associated with lymphoid neoplasia in one study...
2016: PloS One
Maria L Breser, Ruben D Motrich, Leonardo R Sanchez, Virginia E Rivero
BACKGROUND: Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant...
October 4, 2016: Prostate
Ilana C van Rensburg, Chandre Wagman, Kim Stanley, Caroline Beltran, Katharina Ronacher, Gerhard Walzl, Andre G Loxton
Activated B-cells increase T-cell behaviour during autoimmune disease and other infections by means of cytokine production and antigen-presentation. Functional studies in experimental autoimmune encephalomyelitis (EAE) indicate that B-cell deficiencies, and a lack of IL10 and IL35 leads to a poor prognosis. We hypothesised that B-cells play a role during tuberculosis. We evaluated B-cell mRNA expression using real-time PCR from healthy community controls, individuals with other lung diseases and newly diagnosed untreated pulmonary TB patients at three different time points (diagnosis, month 2 and 6 of treatment)...
September 22, 2016: Oncotarget
Petra Cerkovnik, Barbara Jezeršek Novaković, Vida Stegel, Srdjan Novaković
In our previous studies, it has been demonstrated that in more than 80% of mice long-lasting antitumor immunity has been established following intraperitoneal (i.p.) vaccination with tumor vaccine composed of irradiated syngeneic tumor cells and CpG ODNs class C. The aim of this study was, therefore, to investigate molecular mechanisms through which this vaccine triggers the immunity and to define genes particularly involved in this process. Changes in gene expression were followed in mononuclear cells isolated from peritoneal lavages, spleens and bone marrow samples...
September 24, 2016: Molecular Immunology
B V Titov, N A Matveeva, M Yu Martynov, O O Favorova
Carriage frequencies of alleles and genotypes of polymorphic loci of inflammation genes (49A>G CTLA4, 41G>A and 87C>T PDE4D, -590C>T IL4, -308A>G TNF, 252G>A LTA, 874A>T IFNG, -509С>Т, 869T>C and 915G>C TGFB1) were determined in a sample of 200 patients diagnosed with ischemic stroke and in the control group similar in gender and age (146 individuals), all ethnic Russians. The positive association of the allele PDE4D*87C (р = 0.028) and genotype TGFB1*-509Т/Т (р = 0.02) carriage with ischemic stroke was shown...
July 2016: Molekuliarnaia Biologiia
Vanessa Popp, Katharina Gerlach, Stefanie Mott, Agnieszka Turowska, Holger Garn, Raja Atreya, Hans-Anton Lehr, I-Cheng Ho, Harald Renz, Benno Weigmann, Markus F Neurath
BACKGROUND & AIMS: GATA3 is a transcription factor that regulates T-cell production of cytokines. We investigated the role of GATA3 in development of colitis in mice. METHODS: We performed quantitative PCR and immunofluorescence analyses of colon tissues from patients with Crohn's disease (n= 61) or ulcerative colitis (UC, n= 74), or patients without inflammatory bowel diseases (n= 22), to measure levels of GATA3. Colitis was induced by administration of oxazolone or 2,4,6-Trinitrobenzenesulfonic acid (TNBS) to control mice, mice with T-cell specific deletion of GATA3, and mice with deletion of tumor necrosis factor receptor-1 (TNFR1) and TNFR2 (TNFR double knockouts); some mice were given a GATA3-specific DNAzyme (hgd40) or a control DNAzyme via intrarectal administration, or systemic injections of an antibody to TNF prior or during sensitization and challenge phase of colitis induction...
September 14, 2016: Gastroenterology
M Orciani, A Campanati, M Caffarini, G Ganzetti, V Consales, G Lucarini, A Offidani, R Di Primio
BACKGROUND: Atopic dermatitis (AD) is a chronic, and inflammatory disease characterized by a marked imbalance of Th2 versus Th1-Th17 in the early phase of AD, whereas a mixed Th1/Th2 pattern of inflammation is usually found at chronic stage. These features have not been extensively evaluated in undifferentiated skin cells of patients affected by atopic dermatitis (AD). OBJECTIVE: the relative expression of 22 genes encoding for Th1, Th2, and Th17 cytokines and the secretion of the corresponding proteins have been analyzed in Cutaneous Mesenchymal Stem Cells (MSCs) isolated from skin of AD patients (AD-MSCs) to evaluate their role on AD onset...
September 17, 2016: British Journal of Dermatology
Michio Kogame, Hidenari Nagai, Mie Shinohara, Yoshinori Igarashi, Yasukiyo Sumino, Koji Ishii
BACKGROUND/AIM: It has been reported that type 2 helper T-cell (Th2) cytokines down-regulate antitumor immunity, while Th1 cytokines up-regulate it. We previously reported that hepatocarcinogenesis was associated with Th2 dominance in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC), but we did not determine whether Th2 dominance induced carcinogenesis or carcinogenesis led to Th2 dominance. The aim of the study was to clarify whether Th2 dominance induces carcinogenesis or vice versa in patients with HCV-related liver diseases...
September 2016: Anticancer Research
Sefayet Karaca, Ersoy Civelek, Mehmet Karaca, Umit M Sahiner, Riza K Ozgul, Can N Kocabas, Renato Polimanti, Bülent E Sekerel
To dissect the role of immunogenetics in allergy and asthma, we performed a phenome-wide association study in 974 Turkish children selected from a cross-sectional study conducted using ISAAC (International Study of Asthma and Allergies in Children) Phase II tools. We investigated 9 loci involved in different immune functions (ADAM33, ADRB2, CD14, IL13, IL4, IL4R, MS4A2, SERPINE1, and TNF) with respect to 116 traits assessed through blood tests, hypertonic saline challenge tests, questionnaires, and skin prick tests...
2016: Scientific Reports
Tarcio Teodoro Braga, Matheus Correa-Costa, Hatylas Azevedo, Reinaldo Correia Silva, Mario Costa Cruz, Maira Estanislau Soares Almeida, Meire Ioshie Hiyane, Carlos Alberto Moreira-Filho, Marinilce Fagundes Santos, Katia Regina Perez, Iolanda Midea Cuccovia, Niels Olsen Saraiva Camara
INTRODUCTION: Macrophages are heterogeneous and thus can be correlated with distinct tissue outcomes after injury. Conflicting data have indicated that the M2-related phenotype directly triggers fibrosis. Conversely, we hypothesize here that the inflammatory milieu provided by early infiltration of pro-inflammatory macrophages dictates tissue scarring after injury. METHODS AND RESULTS: We first determined that tissue-localized macrophages exhibit a pro-inflammatory phenotype (p40IL12(+)CCR7(+)CD11b(+)) during the early phase of a chronic injury model, in contrast to a pro-resolving phenotype (Arg1(+)IL10(+)CD206(+)CD11b(+)) at a later stage...
September 2016: Immunity, Inflammation and Disease
Allison Kraus, Brent Race, Katie Phillips, Clayton Winkler, Greg Saturday, Michael Kurnellas, Jonathan B Rothbard, Bradley R Groveman, Lawrence Steinman, Byron Caughey
Amyloid hexapeptide molecules are effective in the treatment of the murine model of neuroinflammation, known as experimental autoimmune encephalomyelitis (EAE). Efficacy however differs between two inbred mouse strains, C57BL/6J (B6) and C57BL/10SnJ (B10). Amyloid hexapeptide treatments improved the clinical outcomes of B6, but not B10 mice, indicating that genetic background influences therapeutic efficacy. Moreover, although previous studies indicated that prion protein deficiency results in more severe EAE in B6 mice, we observed no such effect in B10 mice...
September 15, 2016: Journal of Neuroimmunology
Zahra Dorosti, Sepideh Tolouei, Hossein Khanahmad, Rasool Jafari, Fereshteh Jafaee, Seyedeh Marayam Sharafi, Hossein Yousofi Darani
Cystic Echinococcosis is a parasitic disease with cosmopolitan distribution caused by the tape worm Echinococcus granulosus. Fibrous layer is developed around the cyst as a host immune response reaction. The aim of this study was to evaluate the rate of IL-4 gene expression in fibrous layer of bovine and ovine hepatic hydatid cysts using quantitative technique of Real-Time PCR. In this descriptive study the samples of hydatid cyst fibrous layer were taken from 6 bovine and 6 ovine hepatic hydatid cysts. Samples of normal liver tissue close to the cyst were also taken as controls...
September 2016: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
Wei Zhang, Zi Wang, Yunping Luo, Dingrong Zhong, Yufeng Luo, Daobin Zhou
Peripheral T cell lymphoma (PTCL) is an aggressive form of non-Hodgkin's lymphoma characterized by a poor prognosis. In this study, we examined the prognostic value of two T-cell-specific transcription factors, GATA3 and T-bet, in PTCL, uncovered the pathogenesis of PTCL, and investigated new PTCL therapeutic targets. Samples from 109 PTCL patients were examined for expression of GATA3, T-bet and CD68. High GATA3 expression correlated with poor survival in PTCL patients and with tumor-associated macrophage (TAM) infiltration, as indicated by the presence of CD68-positive cells...
August 29, 2016: Oncotarget
Laura Maggi, Gianni Montaini, Alessio Mazzoni, Beatrice Rossettini, Manuela Capone, Maria Caterina Rossi, Veronica Santarlasci, Francesco Liotta, Oliviero Rossi, Oreste Gallo, Raffaele De Palma, Enrico Maggi, Lorenzo Cosmi, Sergio Romagnani, Francesco Annunziato
BACKGROUND: Protection against helminths consists of adaptive responses by TH2 cells and innate responses by group 2 innate lymphoid cells (ILC2s), with these latter being well characterized in mice but less so in human subjects. OBJECTIVE: We sought to characterize human circulating ILC2s and compare their functional profile with that of autologous TH2 cells. METHODS: Circulating ILC2s and TH2 cells were isolated by means of fluorescence-activated cell sorting and magnetic cell sorting and expanded in vitro...
July 27, 2016: Journal of Allergy and Clinical Immunology
Usha Agrawal, Nitu Kumari, Ashwani K Mishra, Pawan Vasudeva, Anup Kumar, Nayan K Mohanty, Sunita Saxena
BACKGROUND: Urothelial carcinoma (UC) is one of most common genitourinary malignancy and the spectrum of disease ranges from in situ lesions to muscle-invasive cancers. The non-muscle-invasive lesions have tendency to recur or progress to muscle-invasive disease. The study of the immune profile may identify immune determinants associated with high-grade, recurrence, and invasion in patients with UC. METHODS: Pathway-focused RT(2) profiler arrays were used to screen patients with UC for dysregulation of candidate genes of Th1-Th2-Th3 and NFκB pathways, which were then validated by real-time polymerase chain reaction on tumor samples and correlated with grade, recurrence, and invasion of tumors to identify their role in predicting behavior of the tumor...
September 2016: Urologic Oncology
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