miRagen begins Phase I trial for MRG-106 to treat cutaneous T-cell lymphoma
US-based miRagen Therapeutics has started a Phase I trial of its anti-cancer product candidate MRG-106, a synthetic microRNA antagonist (LNA antimiR) of microRNA-155, to treat patients with lymphoma.
Conclusions: Single-cell analysis of CTCL skin tumor samples reveals patient-specific landscapes of malignant and reactive lymphocytes within the local microenvironment of each tumor, giving anunprecedented view of lymphocyte heterogeneity and identifying tumor-specific molecular signatures, withimportant implications for diagnosis and personalized disease treatment.
CONCLUSION: HRQoL is significantly more impaired in newly diagnosed female patients with MF/SS and in those with alopecia. As Skindex-29 does not include existential questions on cancer which may cause additional worry and distress, a comprehensive validated CTCL specific questionnaire is urgently needed to more accurately assess disease-specific HRQoL among these patients. This article is protected by copyright. All rights reserved. PMID: 31049926 [PubMed - as supplied by publisher]
In conclusion, we believe that the data presented in this research add new relevant information for a better definition of the pathological states associated with HTLV-1 infection, particularly in relation to the distinct subcellular expression of HBZ in the different pathological contests and related pathologies. Whether HBZ cytoplasmic and nuclear localization in the natural history of HTLV-1 infection represents a marker of infection or is part of the mechanism governing the evolution toward HAM/TSP or ATL is the challenge for future investigation. Author Contributions GF, MB, and RA conceived the work. GF, MB, and AT...
Conclusion: CCL21 induced mTOR activation in MyLa cells, followed by expression of MALAT1, causing cell migration. MALAT1 and mTOR are potential therapeutic targets for MF.
CONCLUSIONS: Single-cell analysis of CTCL skin tumor samples reveals patient-specific landscapes of malignant and reactive lymphocytes within the local microenvironment of each tumor, giving an unprecedented view of lymphocyte heterogeneity and identifying tumor-specific molecular signatures, with important implications for diagnosis and personalized disease treatment. PMID: 31010835 [PubMed - as supplied by publisher]
S ézary syndrome (SS) is an aggressive form of cutaneous T cell lymphoma (CTCL) characterized by involvement of both the skin and the blood. The guarded prognosis for SS reflects a lack of reliably effective therapies. SS patients undergoing treatment often experience transient responses and relapses , supporting the hypothesis that relevant biological heterogeneity exists within the malignant cell population of individual patients. Using single-cell RNA sequencing and machine-learning approaches, we defined a model featuring distinct transcriptomic states within SS.
Thymocyte selection associated high mobility group box 1 (Tox1), a transcription factor that is essential to establish the CD4+ lineage, is overexpressed in malignant cells from patients with CTCL. Knockdown of Tox1 leads to decreased malignant cell viability, while treatment with HDAC inhibitors results in normalization of Tox1expression. Another gene which is consistently overexpressed in patient samples is signal transducers and activators of transcription3 (Stat3), a transcription factor essential for the differentiation of Th17 and follicular helper T cells.
Cutaneous T-cell lymphoma (CTCL) is characterized by resistance to apoptosis involving dysregulation of the FAS ligand (FASL) - FAS death receptor pathway. CTCL cells also exhibit constitutively activated STAT proteins, which are known to upregulate and bind DNA methyltransferases (DNMTs). We hypothesized that, like many other tumor suppressor genes, FAS and FASL expression is at least partially regulated by promoter methylation. Earlier, we showed that methotrexate (MTX), a known folate antagonist, acts as a DNA methylation inhibitor via depleting the methyl donor, S-adenosylmethionine (SAM), in CTCL cells.
Thymocyte selection-associated high mobility group box protein (TOX) is highly enriched in the malignant T cells of cutaneous T cell lymphoma (CTCL). Knocking down its expression resulted in efficient eradication of CTCL cells in culture and in mouse models, suggesting TOX is a desirable target for therapeutic development. Here we describe identification of a novel class of small molecules targeting the DNA binding domain of TOX and evaluation of their ability to inhibit growth and survival of CTCL cells.
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL) primarily arising in the skin. Early diagnosis is difficult as the histology overlaps with features of inflammatory skin diseases. Even when the diagnosis is established there are no prognostic markers that predict whether the disease will be aggressive or indolent. Lastly, there are no curative treatments and MF will invariably relapse even after aggressive chemotherapy. The main objective of this study is to address the presence of intratumor heterogeneity in MF.