A5062130457- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- RNA regulation and disease
- Gut microbiota and health
- Clostridium difficile and Clostridium perfringens research
- Angiogenesis and VEGF in Cancer
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Advanced Biosensing Techniques and Applications
- Virus-based gene therapy research
- Immune cells in cancer
- Multiple Myeloma Research and Treatments
- Dermatology and Skin Diseases
- Influenza Virus Research Studies
- interferon and immune responses
- Immune Response and Inflammation
Sheba Medical Center
2009-2020
Tel Aviv University
2011-2019
Nara Medical University
2012
Melanoma Institute Australia
2011
New fecal microbiota for cancer patients The composition of the gut microbiome influences response to immunotherapies. Baruch et al. and Davar report first-in-human clinical trials test whether transplantation (FMT) can affect how metastatic melanoma respond anti–PD-1 immunotherapy (see Perspective by Woelk Snyder). Both studies observed evidence benefit in a subset treated patients. This included increased abundance taxa previously shown be associated with anti–PD-1, CD8 + T cell...
Some solid tumors have reduced posttranscriptional RNA editing by adenosine deaminase acting on (ADAR) enzymes, but the functional significance of this alteration has been unclear. Here, we found primary RNA-editing enzyme ADAR1 is frequently in metastatic melanomas. In situ analysis melanoma samples using progression tissue microarrays indicated a substantial downregulation during transition. Further, knockdown altered cell morphology, promoted vitro proliferation, and markedly enhanced...
MicroRNAs (miRNAs) are small non-coding RNAs with regulatory roles, which involved in a broad spectrum of physiological and pathological processes, including cancer. A common strategy for identification miRNAs cell transformation is to compare malignant cells normal cells. Here we focus on that regulate the aggressive phenotype melanoma To avoid differences due genetic background, comparative high-throughput miRNA profiling was performed two isogenic human lines display major their net...
CEACAM1 (biliary glycoprotein-1, CD66a) was reported as a strong clinical predictor of poor prognosis in melanoma. We have previously identified tumor escape mechanism from cytotoxic lymphocytes. Here, we present substantial evidence vitro and vivo that blocking function with novel monoclonal antibody (MRG1) is promising strategy for cancer immunotherapy. MRG1, murine IgG1 antibody, raised against human CEACAM1. It recognizes the CEACAM1-specific N-domain high affinity (K(D) ~ 2 nmol/L)....
Vasculogenic mimicry (VM) describes functional vascular channels composed only of tumor cells and its presence predicts poor prognosis in melanoma patients. Inhibition this alternative vascularization pathway might be clinical importance, especially as several anti-angiogenic therapies targeting endothelial are largely ineffective melanoma. We show the VM structures histologically a series human lesions demonstrate that cell cultures derived from these form tubes 3D ex vivo. tested ability...
Melanoma cells use different migratory strategies to exit the primary tumor mass and invade surrounding subsequently distant tissues. We reported previously that ADAR1 expression is downregulated in metastatic melanoma, thereby facilitating proliferation. Here we show silencing enhances melanoma cell invasiveness ITGB3 expression. The enhanced invasion reversed when blocked with antibodies. Re-expression of wild-type or catalytically inactive establishes this mechanism as independent RNA...
The prognostic value of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in melanoma was demonstrated more than a decade ago as superior to Breslow score. We have previously shown that intercellular homophilic CEACAM1 interactions protect cells from lymphocyte-mediated elimination. Here, we study direct effects on biology. By employing tissue microarrays and low-passage primary cultures metastatic melanoma, show expression gradually increases nevi specimens, with strong...
Natural killer (NK) cells have long been considered as potential agents for adoptive cell therapy solid cancer patients. Until today most studies utilized autologous NK and yielded disappointing results. Here we analyze various modular strategies to employ allogeneic transfer, including donor-recipient HLA-C mismatching, selective activation induction of melanoma-recognizing lysis receptors, co-administration antibodies elicit antibody-dependent cytotoxicity (ADCC). We show that the relevant...
The search for melanoma biomarkers is crucial, as the incidence of continues to rise. We have previously demonstrated that serum CEACAM1 (sCEACAM1) secreted from cells and correlates with disease progression in metastatic patients. Here, we used a different cohort patients regional or (N = 49), treated autologous vaccination. By monitoring sCEACAM1 samples obtained prior after vaccination, show state, overall survival, S100B. trend change following vaccination (increase/decrease) inversely...
// Shira Ashkenazi 1,2 , Rona Ortenberg 1 Michal Besser Jacob Schachter 1,* and Gal Markel 1,2,3,* Ella Lemelbaum Institute of Melanoma, Sheba Medical Center, Ramat Gan, Israel 2 Department Clinical Microbiology Immunology, Sackler Faculty Medicine, Tel Aviv University, 3 Talpiot Leadership program, * These authors have contributed equally to this work Correspondence to: Markel, email: Keywords : CEACAM1, melanoma, SOX9, T cells, Immune checkpoint, Immunology Section, response, Immunity...
Background NK cells are key players in anti tumor immune response, which can be employed cell-based therapeutic modalities. One of the suggested ways to amplify their effect, especially field stem cell transplantation, is by selecting donor/recipient mismatches specific HLA, reduce inhibitory effect killer Ig-like receptors (KIRs). Here we suggest an alternative approach for augmentation allogeneic cells, founded on profile matching donor lysis (NKLR) phenotype with lysis-ligands....
Cells in our body can induce hundreds of antiviral genes following virus sensing, many which remain largely uncharacterized. CEACAM1 has been previously shown to be induced by various innate systems; however, the reason for such tight integration sensing systems was not apparent. Here, we show that is detection HCMV and influenza viruses their respective DNA RNA sensors, IFI16 RIG-I. This induction mediated IRF3, bound an ISRE element present human, but mouse, promoter. Furthermore,...
BRAF becomes constitutively activated in 50% to 70% of melanoma cases. CEACAM1 has a dual role melanoma, including facilitation cell proliferation and suppression infiltrating lymphocytes, which are consistent with its value as marker for poor prognosis patients. Here we show that BRAFV600E cells treated MEK inhibitors (MAPKi) downregulate mRNA protein expression dose- exposure time-dependent manners. Indeed, there is significant correlation between the presence specimens obtained from 45...
Malignant melanoma is a devastating disease whose incidences are continuously rising. The recently approved antimelanoma therapies carry new hope for metastatic patients the first time in decades. However, clinical management of severely hampered by absence effective screening tools. expression CEACAM1 adhesion molecule on cells strong predictor poor prognosis. Interestingly, melanoma-secreted form (sCEACAM1) has emerged as potential tumor biomarker. Here we add novel evidences supporting...
Abstract Background: The majority of metastatic melanoma patients treated with Programed cell Death (PD)-1 blockade fail to achieve durable response. gut microbiota profoundly affects host immunity, and fecal transplantations (FMT), which transfers the entire from one another, has been shown enhance anti-PD-1 effectiveness in murine models. We report initial safety efficacy results first three on a Phase I study FMT re-induction therapy refractory melanoma. Methods: donors were two who...
Abstract A new method of detecting and diagnosing melanoma based on biomarker was developed its feasibility demonstrated. The is an electrochemical biosensor platform comprised a special biochip device, performing multi‐channel amperometric detection the enzymatic activity tyrosinase, enzyme melanoma. newly able to electrochemically detect tyrosinase in fresh biopsy samples. This bioelectrochemical rapid, yielding results within minutes from removal. Using “as is” samples, without...
Carcinoembryonic antigen cell adhesion molecule (CEACAM)-1 is a multi-functional protein, with strong predictive value for poor prognosis when found in primary cutaneous melanoma lesions. In this study, the expression of CEACAM1 uveal was correlated clinicopathologic parameters.CEACAM1 immunohistochemically evaluated 79 melanomas and 21 liver metastases patients who were treated at Hadassah-Hebrew University Medical Center between years 1986 2006. The findings location, type, extracellular...