Molecular Pathways of Interleukin-13 in Cutaneous T-cell Lymphoma
Molecular Pathways of Interleukin-13 in Cutaneous T-cell Lymphoma
批准号:
9178480
负责人:
PATRIZIA FUSCHIOTTI
金额:
$21.16万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-07-01 至 2018-06-30
关键词:
AffectBloodCell ProliferationCellsClinicClinicalCutaneousDiagnosisDiseaseDisease ProgressionEarly DiagnosisExfoliative DermatitisFatal OutcomeGenesGenetic TranscriptionIL-13Ralpha1Immune responseImmunofluorescence MicroscopyIn VitroIndolentInnovative TherapyInterleukin-13LeadLeukemic CellLightLymphLymphatic DiseasesMalignant - descriptorMalignant NeoplasmsMediatingMental DepressionMolecularMolecular ProfilingMolecular TargetMycosis FungoidesOrgan Culture TechniquesOutcomePathogenesisPathway interactionsPatientsPatternPhasePrimary NeoplasmProductionProteinsRoleRunningSTAT6 Transcription FactorSezary SyndromeSignal PathwaySignal TransductionSignaling MoleculeSiteSkinSkin NeoplasmsSmall Interfering RNAStagingSurvival RateT-Cell LymphomaT-LymphocyteTimeabstractingautocrinebasecancer cellcell transformationclinically relevantcytokinegenome-wideinhibitor/antagonistinsightknock-downmalignant lymphocytememory CD4 T lymphocyteneoplastic cellnovel diagnosticsnovel markeroutcome forecastperipheral bloodpreventreceptorskin lesiontargeted treatmenttumor
中文摘要
摘要
皮肤T细胞淋巴瘤(CTCL)是一组异质性的T淋巴细胞
主要影响皮肤的恶性肿瘤。蕈样肉芽肿(MF)是最常见的
CTCL的形式,并且通常进行惰性课程。然而,在相当数量的
病人的疾病可能会进展和肿瘤细胞扩散到身体的其他部位
导致致命的后果。MF的诊断,特别是在早期阶段,很难,
由于缺乏恶性淋巴细胞的特异性标志物,有限
晚期MF患者有治疗选择,这反映了
对疾病的发病机理认识不足。
我们最近证明IL-13及其受体代表了一种新的肿瘤标志物,
恶性MF。我们的研究进一步表明IL-13信号通过信号转导途径。
转导和转录激活因子-6(STAT-6)蛋白。值得注意的是,我们发现
MF患者受影响皮肤中大量活化STAT-6+细胞,
处于晚期在这里,我们建议分析IL-13的分子途径,
恶性细胞中来自侵袭性MF的信号传导。我们的核心假设是
STAT-6是MF发病机制中的一个主要因素,其在促进MF发病中起关键作用。
疾病进展并代表治疗的潜在靶点。具体
本提案的目的是牢固地建立在我们以前的成果基础上,并侧重于确定
STAT-6在MF发病机制中的独特作用,从而阐明了
MF中IL-13诱导肿瘤细胞增殖的分子机制
确定MF发病机制将揭示新的诊断剂,
分子靶点,导致针对这种疾病的创新疗法。
英文摘要
Abstract
Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of T lymphocytes
malignancies that primarily affect skin. Mycosis fungoides (MF) is the most common
form of CTCL and typically runs an indolent course. However, in a significant number of
patients the disease may progress and tumor cells spread to other sites of the body
leading to a fatal outcome. Diagnosis of MF, especially in the early stages, is difficult to
establish due to the absence of specific markers for malignant lymphocytes. Limited
treatment options are available for patients with advanced-stage MF, a reflection of the
poor understanding of disease pathogenesis.
We have recently demonstrated that IL-13 and its receptors represent novel markers of
malignancy in MF. Our studies further implicated IL-13 signaling via the Signal
Transducer and Activator of Transcription-6 (STAT-6) protein. Significantly, we found
high numbers of activated STAT-6+ cells in the affected skin of MF patients, particularly
in advanced stages. Here we propose to analyze the molecular pathways of IL-13
signaling in malignant cells from aggressive forms of MF. Our central hypothesis is that
STAT-6 is a major factor in the pathogenesis of MF that is critical in promoting
disease progression and represents a potential target for therapy. The Specific
Aims of this proposal are based solidly on our previous results and focus on identifying
the unique role of STAT-6 in the pathogenesis of MF, thus shedding light on the
molecular mechanisms underlying IL-13-induced tumor cell proliferation in MF.
Identifying the mechanisms of MF pathogenesis will reveal novel diagnostic agents and
molecular targets, leading to innovative therapies against this disease.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Pathogenesis of systemic sclerosis: role of the skin-resident CD8+ T cells
-
批准号:9121463
-
项目类别:
-
资助金额:$7.7万
-
财政年份:2014
-
负责人:PATRIZIA FUSCHIOTTI
-
依托单位:
Pathogenesis of systemic sclerosis: role of the skin-resident CD8+ T cells
-
批准号:8910637
-
项目类别:
-
资助金额:$7.7万
-
财政年份:2014
-
负责人:PATRIZIA FUSCHIOTTI
-
依托单位:
Pathogenesis of systemic sclerosis: role of the skin-resident CD8+ T cells
-
批准号:8769486
-
项目类别:
-
资助金额:$7.7万
-
财政年份:2014
-
负责人:PATRIZIA FUSCHIOTTI
-
依托单位:
海外基金