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Building An Animal Model Of Breast Cancer Bone Metastasis And Relative MicroRNA Analysis The Role Of Sentinel Lymph Node Biopsy For Melanoma Of Extremity

Posted on:2015-10-12Degree:MasterType:Thesis
Country:ChinaCandidate:Z B YeFull Text:PDF
GTID:2284330431976173Subject:Oncology
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MicroRNAs (miRNAs) are a class of conserved non-coding20-22-nucleotide (nt) length small RNAs, which can regulate gene expression post-transcriptionally by interacting with the3’untranslated regions (3’UTR) of target mRNAs. It is presumable that about40%of the genes are regulated by miRNAs. Accumulating evidence indicates that miRNAs are involved in regulating cancer invasion and metastasis. An increasing number of researches demonstrate that miRNAs can promote or inhibit cellular motility depending on genetic backgrounds of different cancers and changing microenvironments.Recent investigations in the field of cancer cell metastasis rely heavily on the availability of in vivo animal models. An ideal animal model could mimic the process of cancer cells developing spontaneously to distant organs. In this study, we established an in vivo bone metastasis model of breast cancer by injecting MDA-MB-231cells into the left ventricle of nude mice, and then screened the differentially expressed miRNAs between parental and bone-metastatic MDA-MB-231cells using miRNA array.Among the detected miRNAs,118miRNAs manifested differential expressions between parental and bone-metastatic MDA-MB-231cells, of which16upregulated whereas102downregulated more than two folds (p<0.05). Especially, miR-429was probably implicated into negatively regulating bone metastasis of breast cancer cells. Furthermore, overexpression of miR-429in MDA-MB-231cells derived from bone metastatic lesions remarkably suppressed invasion in vitro. In addition, we identified ZEB1and CRKL as potential targets of miR-429by combined analyzing results from in silico search (Targetsan, DIANA-microT and microRNA.ORG et al) and global expression array of the same RNA samples. Moreover, immunoblot assay confirmed that miR-429could reduce ZEB1at protein level. Taken together, our results offer an opportunity for further understanding of the recondite mechanisms underlying the bone metastasis of breast cancer. Objective To evaluate the role of sentinel lymph node biopsy(SLNB) for melanoma of extremity.Methods From April2007to August2013, forty-eight (25men,23women) cases of melanoma of extremity were treated with sentinel lymph node biopsy. Median patient age was51.7years (range from17to74years). Of the lesions,30located on sole of the foot,4on the toe,3on the back of foot,3beneath the nail,4on the hand,2on the thigh,1on the popliteal area and the elbow respectively.All the cases were performed with sentinel lymph node biopsy and wide resection.37cases were underwent limb savage surgery, while11cases were underwent amputation. Of the cases with limb salvage,28cases underwent free skin grafting or local flap grafting reconstruction after wide resection. Of the surgical margin, wide resection was performed on37cases, and radical resection was performed on11cases. After the surgery, adjuvant chemotherapy was performed on9cases,and adjuvant biotherapy of interferon and interleukin was performed on26cases. Except for2cases,46cases were followed up, with the mean follow-up period being20.1months (range from2to60months).Results39(81.25%) cases had negative result of SLNB, while9(18.75%) cases was positive.Recurrence or metastasis was more common in those with positive SLNB (3of9cases/33.3%) compared to those with negative SLNB (4of39cases/10.3%).Patients with negative result had a significantly better disease free survival compared with the positive(P=0.03). Otherwise sex and age showed no significant difference in disease free survival.Conclusion Sentinel lymph node biopsy enable us to have a better understanding of regional lymph node through lymphoscintigraphy.It improves the accuracy of staging and provides valuable prognostic information to guide subsequent treatment decisions.
Keywords/Search Tags:miR-429, ZEB1, breast cancer bone metastasis, animal modelmelanoma, sentinel lymph node biopsy, disease free survival
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