Pre-metastatic Omental Niche Formation in Ovarian Cancer
卵巢癌转移前网膜微环境的形成
基本信息
- 批准号:10117199
- 负责人:
- 金额:$ 37.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdipocytesCancer ModelCancer PatientCause of DeathCell DeathCell Differentiation processCellsClinicalClinical ManagementCommunicable DiseasesConsumptionCystic FibrosisDNADeoxyribonucleasesDevelopmentDiseaseEnzymesFatty acid glycerol estersFibroblastsGenetic ModelsGoalsGreater sac of peritoneumGrowthHumanImmuneImplantInfectionInflammatoryInternetIntestinal ObstructionIntestinesKnockout MiceMalignant NeoplasmsMalignant neoplasm of ovaryMesothelial CellMetastatic Malignant Neoplasm to the OvaryMicrobeModelingMusNeoplasm MetastasisOmentumPatientsPharmaceutical PreparationsPharmacologyProtein-arginine deiminaseRecombinantsRiskRoleSiteSpecimenStomachStromal CellsTimeTissuesTropismVisceral fatWomanWorkXenograft Modelbasecancer cellcancer therapychemotherapycost effectivedrug repurposingeffective therapyexperienceextracellularimplantationinhibitor/antagonistinsightmacrophagemultidisciplinaryneutrophilnovelnovel therapeuticsovarian neoplasmresponsestemtumortumor growthtumor progression
项目摘要
Bowel obstruction is a leading cause of death in women with ovarian cancer and often stems from growth of
tumors on the omentum, a fat pad that suspends from the stomach. The objective of this project is to determine
the mechanisms that cause ovarian cancer cells to implant on the omentum, with the overarching goal of
identifying more effective therapies for this lethal disease. Previous studies of ovarian cancer metastasis have
mostly focused on investigating interactions of cancer cells with adipocytes, macrophages, fibroblasts and
mesothelial cells. However, as these stromal cells are constituents of all visceral fat pads, interactions with
these cells may not fully explain the tropism of ovarian cancer cells for the omentum. Neutrophils act as the
first line of defense in response to infection or malignancy. Because the omentum is the major site of neutrophil
influx into the peritoneal cavity, we speculate that neutrophils direct ovarian cancer cells to the omental niche.
This study focuses on a phenomenon in which neutrophils extrude sticky DNA webs called neutrophil
extracellular traps (NETs). NETs were originally discovered to trap microbes in infectious diseases but very
little is known about the significance of NETs in cancer. Based on our preliminary studies, we hypothesize that
ovarian cancer cells induce neutrophils to form NETs in the omentum, and that omental metastasis stems in
part from entrapment of cancer cells by NETs in the omental niche. In this project, we will determine whether
(1) ovarian cancers induce NET formation in the pre-metastatic omental niche, (2) omental metastasis of
ovarian cancer depends on NET formation and (3) omental metastasis is decreased by treatment with agents
that inhibit NETs. These aims will be accomplished by evaluating patient clinical specimens, mouse tumor
models and genetically modified mice that are defective in NET formation. Our study will provide new and
provocative insights into the mechanisms that drive the propensity of ovarian cancer to colonize the omentum
and the potential of repurposing NET-inhibiting agents for ovarian cancer therapy.
肠梗阻是卵巢癌女性患者的主要死亡原因,通常源于卵巢癌的生长。
大网膜上的肿瘤,一种悬挂在胃上的脂肪垫。该项目的目标是确定
导致卵巢癌细胞植入大网膜的机制,其首要目标是
为这一致命疾病寻找更有效的治疗方法。以前对卵巢癌转移的研究已经
主要集中在研究癌细胞与脂肪细胞、巨噬细胞、成纤维细胞和
间皮细胞。然而,由于这些基质细胞是所有内脏脂肪垫的组成部分,与
这些细胞可能不能完全解释卵巢癌细胞对大网膜的趋向性。中性粒细胞扮演着
应对感染或恶性疾病的第一道防线。因为大网膜是中性粒细胞的主要部位
中性粒细胞进入腹膜腔后,我们推测是中性粒细胞将卵巢癌细胞导向大网膜小窝。
这项研究的重点是中性粒细胞排出一种叫做中性粒细胞的粘性dna网络。
胞外陷阱(Net)。蚊帐最初被发现用来捕获传染病中的微生物,但非常
人们对Nets在癌症中的重要性知之甚少。根据我们的初步研究,我们假设
卵巢癌细胞诱导中性粒细胞在大网膜形成Net,大网膜转移源于
部分原因是由大网膜壁龛内的网络捕获癌细胞所致。在这个项目中,我们将确定是否
(1)卵巢癌在转移前的大网膜壁龛中诱导净形成;(2)大网膜转移
卵巢癌依赖于净形成;(3)药物治疗可减少大网膜转移
这抑制了篮网。这些目标将通过评估患者的临床标本、小鼠肿瘤来实现
网络形成有缺陷的模型和转基因小鼠。我们的研究将提供新的和
对驱使卵巢癌倾向于大网膜定植的机制的具有挑衅性的见解
以及用于卵巢癌治疗的再利用网络抑制剂的潜力。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Honami Naora其他文献
Honami Naora的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Honami Naora', 18)}}的其他基金
Boosting anti-tumor immunity in the omentum for metastasis prevention
增强大网膜的抗肿瘤免疫力以预防转移
- 批准号:
10648192 - 财政年份:2023
- 资助金额:
$ 37.41万 - 项目类别:
Isolation of miRNA-rich extracellular vesicles for liquid biopsy
分离富含 miRNA 的细胞外囊泡用于液体活检
- 批准号:
10579299 - 财政年份:2022
- 资助金额:
$ 37.41万 - 项目类别:
Isolation of miRNA-rich extracellular vesicles for liquid biopsy
分离富含 miRNA 的细胞外囊泡用于液体活检
- 批准号:
10431224 - 财政年份:2022
- 资助金额:
$ 37.41万 - 项目类别:
Impact of diagnostic peritoneal lavage on omentum metastasis
诊断性腹腔灌洗对大网膜转移的影响
- 批准号:
10286303 - 财政年份:2021
- 资助金额:
$ 37.41万 - 项目类别:
Impact of diagnostic peritoneal lavage on omentum metastasis
诊断性腹腔灌洗对大网膜转移的影响
- 批准号:
10447751 - 财政年份:2021
- 资助金额:
$ 37.41万 - 项目类别:
Pre-metastatic Omental Niche Formation in Ovarian Cancer
卵巢癌转移前网膜微环境的形成
- 批准号:
10360586 - 财政年份:2018
- 资助金额:
$ 37.41万 - 项目类别:
Pre-metastatic Omental Niche Formation in Ovarian Cancer
卵巢癌转移前网膜微环境的形成
- 批准号:
9903259 - 财政年份:2018
- 资助金额:
$ 37.41万 - 项目类别:
Mechanism of evasion by ovarian cancers from anti-VEGF therapy
卵巢癌逃避抗 VEGF 治疗的机制
- 批准号:
9302312 - 财政年份:2016
- 资助金额:
$ 37.41万 - 项目类别:
Mechanism of evasion by ovarian cancers from anti-VEGF therapy
卵巢癌逃避抗 VEGF 治疗的机制
- 批准号:
9152040 - 财政年份:2016
- 资助金额:
$ 37.41万 - 项目类别:
Stromal Interactions and Leukemic Risk in Myelodysplastic Syndromes
骨髓增生异常综合征中的基质相互作用和白血病风险
- 批准号:
8897103 - 财政年份:2015
- 资助金额:
$ 37.41万 - 项目类别:
相似海外基金
Treatment research by the suppression of secretory phenomenon associated with cellular senescence in mouse prostate cancer model
通过抑制小鼠前列腺癌模型中与细胞衰老相关的分泌现象进行治疗研究
- 批准号:
21K09409 - 财政年份:2021
- 资助金额:
$ 37.41万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Pancreatic cancer biomarker research by the exosome proteome analysis of the HGD rat pancreatic cancer model
HGD大鼠胰腺癌模型的外泌体蛋白质组分析研究胰腺癌生物标志物
- 批准号:
21K07910 - 财政年份:2021
- 资助金额:
$ 37.41万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identifying and manipulating molecular mechanisms controlling cancer stem cell metastatic potential in a human oral cancer model.
识别和操纵控制人类口腔癌模型中癌症干细胞转移潜力的分子机制。
- 批准号:
MR/V009494/1 - 财政年份:2021
- 资助金额:
$ 37.41万 - 项目类别:
Research Grant
Establishment of near-infrared photoimmunotherapy targeting CD73 using mouse lung cancer model
小鼠肺癌模型建立靶向CD73的近红外光免疫疗法
- 批准号:
21K07189 - 财政年份:2021
- 资助金额:
$ 37.41万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Synthetic Lethality Related to Over-Expression of Telomerase Reverse Transcriptase in a Prostate Cancer Model
前列腺癌模型中与端粒酶逆转录酶过度表达相关的合成致死率
- 批准号:
467101 - 财政年份:2021
- 资助金额:
$ 37.41万 - 项目类别:
Studentship Programs
Development of a Vascularized Brain Cancer Model with Built-in Immunity and Lymphatic System for Immune Cell/Drug Delivery and Clearance
开发具有内置免疫和淋巴系统的血管化脑癌模型,用于免疫细胞/药物输送和清除
- 批准号:
565148-2021 - 财政年份:2021
- 资助金额:
$ 37.41万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Master's
Characterizing the Behaviour of Myeloid-Derived Suppressor Cells in a 3D In Vitro cancer Model
表征 3D 体外癌症模型中骨髓源性抑制细胞的行为
- 批准号:
551138-2020 - 财政年份:2020
- 资助金额:
$ 37.41万 - 项目类别:
University Undergraduate Student Research Awards
Patient Derived Cancer Model (PDCM) Finder
患者衍生癌症模型 (PDCM) 查找器
- 批准号:
10260591 - 财政年份:2020
- 资助金额:
$ 37.41万 - 项目类别:
Establishment of visualizing oral cancer model and development of clinical ultrasonographic examination which detects initial cervical metastatic lymph node by oral cancer
可视化口腔癌模型的建立及口腔癌早期颈部转移淋巴结临床超声检查的进展
- 批准号:
20K10140 - 财政年份:2020
- 资助金额:
$ 37.41万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Advancing precision medicine through development of the canine comparative cancer model
通过开发犬类比较癌症模型推进精准医疗
- 批准号:
9910776 - 财政年份:2020
- 资助金额:
$ 37.41万 - 项目类别: