Cancer in the Immunosuppressed Host
免疫抑制宿主的癌症
基本信息
- 批准号:9768990
- 负责人:
- 金额:$ 8.36万
- 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:2018-09-01 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAgingAllogenicBiologicalBiological AssayBlood specimenCanis familiarisCarcinomaCase StudyCellsChildChronicDNAFamily memberFemaleFetusFluorescent in Situ HybridizationGenetic PolymorphismGenotypeHealthHealth BenefitHeart TransplantationHomologous TransplantationHumanImmunocompromised HostImmunohistochemistryImmunosuppressionIndividualKidney TransplantationLeadLifeMalignant NeoplasmsMothersOrgan DonorOrgan TransplantationPatientsPersonsPhenotypePhenotypic SexPregnancyRecurrenceReportingResearch DesignResectedSNP arraySourceSpecimenSquamous CellSquamous cell carcinomaSwabTestingTransplant RecipientsWomanX ChromosomeY Chromosomedesignexperimental studyfetus cellhuman leukocyte antigen testingkeratinocytemalemortalityoffspringperipheral bloodpregnantrecruitresidencesextumor
项目摘要
PROJECT SUMMARY/ABSTRACT
Cells exchanged between a mother and fetus during pregnancy are now known to establish long-term
residence in the other individual creating a legacy of maternal cells in her progeny and cells of fetal origin in
women who have been pregnant. The capacity for these naturally acquired cells to confer health benefits is
supported by experimental and human studies. However detrimental effects on health may also sometimes
occur. Transmissible cancer has been reported in dogs, Tasmanian devils, and in case reports in humans,
primarily as mother to offspring transfer. To our knowledge no prior study has asked or addressed the
possibility that naturally acquired allogeneic cells could sometimes be the source of a malignancy. Asking
when this might occur led to this proposal. Patients who undergo organ transplantation are subject to long-term
chronic immune suppression. Organ transplant recipients (OTR) are afflicted by multiple, frequently arising,
squamous cell keratinocyte carcinomas (SCC). Recurrence rates and mortality related to SCC are significantly
increased compared to non-immunosuppressed individuals. The purpose of this R03 application is to
investigate SCC in OTR for allogeneic DNA and cells. Aim 1 will begin by interrogating DNA extracted from
OTR SCCs by quantitative PCR (qPCR) for a Y-chromosome specific sequence; disproportionate absence of
male DNA in tumors from males or presence of male DNA in tumors from females will be considered potential
evidence for allogeneic cancer. Cellular studies will next be done by combined fluorescence in situ
hybridization (FISH) with Y- and X-chromosome specific probes and concomitant immunohistochemistry (IHC)
to identify, quantify, and phenotype sex-mismatched cells in tumor specimens. Aim 2 will investigate OTR
SCCs to determine the specific origin of allogeneic DNA and cells detected in Aim 1. In part 1 of Aim 2 family
members will be recruited so HLA and other polymorphism genotyping can be conducted. Results will be
evaluated to identify a non-shared HLA (or other) polymorphism unique to the family member. DNA extracted
from the tumor specimen will be quantitatively interrogated for the non-shared polymorphism selecting from a
panel of HLA- and other polymorphism-specific qPCR assays we have developed for this purpose. qPCR
testing will include an assay to detect donor origin DNA in tumors. For patients for whom family members are
not available, Aim 2 part 2 will conduct SNP arrays and analysis of paired tumor and peripheral blood samples
to determine whether tumor DNA is autochthonous or allogeneic in origin.
项目总结/摘要
现在已知,在怀孕期间母亲和胎儿之间交换的细胞可以建立长期的
居住在另一个人创造了一个遗产的母体细胞在她的后代和细胞的胎儿来源,
已经怀孕的妇女。这些自然获得的细胞赋予健康益处的能力是
得到了实验和人体研究的支持。然而,对健康的有害影响有时也可能
发生.据报道,狗、袋獾和人类都患有传染性癌症,
主要是由母亲传给后代。据我们所知,之前没有研究询问或解决过
自然获得的同种异体细胞有时可能是恶性肿瘤的来源。问
这可能导致了这个提议。接受器官移植的病人,
慢性免疫抑制器官移植受者(OTR)患有多种,经常出现,
鳞状细胞角化细胞癌(SCC)。与SCC相关的复发率和死亡率显著高于
与非免疫抑制个体相比增加。此R 03应用程序的目的是
研究OTR中SCC的同种异体DNA和细胞。目标1将开始通过询问DNA提取从
通过定量PCR(qPCR)检测Y染色体特异性序列的OTR SCC;
男性肿瘤中的男性DNA或女性肿瘤中存在男性DNA将被视为潜在的
同种异体癌的证据接下来将通过结合原位荧光进行细胞研究
Y和X染色体特异性探针杂交(FISH)和伴随免疫组织化学(IHC)
鉴定、定量和表型肿瘤标本中性别不匹配的细胞。Aim 2将调查OTR
SCC以确定Aim 1中检测到的同种异体DNA和细胞的特定来源。在Aim 2系列的第1部分中
将招募成员,以便进行HLA和其他多态性基因分型。结果将
评估以鉴定家族成员特有的非共享HLA(或其他)多态性。提取的DNA
将从肿瘤样本中定量询问非共享多态性,
我们为此目的开发了一组HLA和其他多态性特异性qPCR测定。qPCR
测试将包括检测肿瘤中供体来源DNA的分析。对于家庭成员
目标2第2部分将对配对的肿瘤和外周血样本进行SNP阵列和分析
以确定肿瘤DNA是自体的还是同种异体的。
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)
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J. Lee Nelson其他文献
Forward and reverse inheritance — the yin and the yang
正向和反向继承——阴与阳
- DOI:
10.1038/nrrheum.2017.88 - 发表时间:
2017-06-08 - 期刊:
- 影响因子:32.700
- 作者:
J. Lee Nelson;Nathalie C. Lambert - 通讯作者:
Nathalie C. Lambert
133: At diagnosis, total cell-free DNA concentration is elevated in preeclampsia versus controls
- DOI:
10.1016/j.ajog.2019.11.149 - 发表时间:
2020-01-01 - 期刊:
- 影响因子:
- 作者:
Teodora Kolarova;J. Lee Nelson;Hilary Gammill;Christina Lockwood;Raj Shree - 通讯作者:
Raj Shree
Microchimerism detection by human leucocyte antigen‐specific quantitative‐polymerase chain reaction analysis in recipients of allogeneic Epstein–Barr virus‐specific cytotoxic T lymphocytes
在同种异体 Epstein-Barr 病毒特异性细胞毒性 T 细胞淋巴受者中通过人白细胞抗原特异性定量聚合酶链反应分析检测微嵌合
- DOI:
10.1111/j.1365-2141.2005.05460.x - 发表时间:
2005 - 期刊:
- 影响因子:6.5
- 作者:
K. Lucas;J. Lee Nelson;Timothy D. Erickson;Qi Sun - 通讯作者:
Qi Sun
J. Lee Nelson的其他文献
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{{ truncateString('J. Lee Nelson', 18)}}的其他基金
Transgenerational Microchimerism in Pregnancy Loss
妊娠失败中的跨代微嵌合现象
- 批准号:
7306029 - 财政年份:2007
- 资助金额:
$ 8.36万 - 项目类别:
Transgenerational Microchimerism in Pregnancy Loss
妊娠失败中的跨代微嵌合现象
- 批准号:
7484075 - 财政年份:2007
- 资助金额:
$ 8.36万 - 项目类别:
HLA Alleles, Self-Peptides and Microbial Mimicry in SSc
SSc 中的 HLA 等位基因、自肽和微生物拟态
- 批准号:
6407027 - 财政年份:2001
- 资助金额:
$ 8.36万 - 项目类别:
HLA Alleles, Self-Peptides and Microbial Mimicry in SSc
SSc 中的 HLA 等位基因、自肽和微生物拟态
- 批准号:
6607038 - 财政年份:2001
- 资助金额:
$ 8.36万 - 项目类别:
HLA Alleles, Self-Peptides and Microbial Mimicry in SSc
SSc 中的 HLA 等位基因、自肽和微生物拟态
- 批准号:
6760840 - 财政年份:2001
- 资助金额:
$ 8.36万 - 项目类别:
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